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1. Mixed responses to targeted therapy driven by chromosomal instability through p53 dysfunction and genome doubling

Author: Hobor, S, Al Bakir, M, Hiley, C, Skrzypski, M, Frankell, A, Bakker, B, Watkins, T, Markovets, A, Dry, J, Brown, A, van der Aart, J, van den Bos, H, Spierings, D, Oukrif, D, Novelli, M, Chakrabarti, T, Rabinowitz, A, Ait Hassou, L, Litiere, S, Kerr, D, Tan, L, Kelly, G, Moore, D, Renshaw, M, Venkatesan, S, Hill, W, Huebner, A, Martinez-Ruiz, C, Black, J, Wu, W, Angelova, M, Mcgranahan, N, Downward, J, Chmielecki, J, Barrett, C, Litchfield, K, Chew, S, Blakely, C, de Bruin, E, Foijer, F, Vousden, K, Bivona, T, Lester, J, Bajaj, A, Nakas, A, Sodha-Ramdeen, A, Tufail, M, Scotland, M, Boyles, R, Rathinam, S, Wilson, C, Marrone, D, Dulloo, S, Fennell, D, Matharu, G, Shaw, J, Boleti, E, Cheyne, H, Khalil, M, Richardson, S, Cruickshank, T, Price, G, Kerr, K, Benafif, S, French, J, Gilbert, K, Naidu, B, Patel, A, Osman, A, Enstone, C, Langman, G, Shackleford, H, Djearaman, M, Kadiri, S, Middleton, G, Leek, A, Hodgkinson, J, Totton, N, Montero, A, Smith, E, Fontaine, E, Granato, F, Paiva-Correia, A, Novasio, J, Rammohan, K, Joseph, L, Bishop, P, Shah, R, Moss, S, Joshi, V, Crosbie, P, Brown, K, Carter, M, Chaturvedi, A, Oliveira, P, Lindsay, C, Blackhall, F, Krebs, M, Summers, Y, Clipson, A, Tugwood, J, Kerr, A, Rothwell, D, Dive, C, Aerts, H, Schwarz, R, Kaufmann, T, Wilson, G, Rosenthal, R, Van Loo, P, Birkbak, N, Szallasi, Z, Kisistok, J, Sokac, M, Salgado, R, Diossy, M, Demeulemeester, J, Bunkum, A, Dwornik, A, Magness, A, Rowan, A, Karamani, A, Toncheva, A, Chain, B, Castignani, C, Bailey, C, Abbosh, C, Puttick, C, Weeden, C, Lee, C, Richard, C, Naceur-Lombardelli, C, Pearce, D, Karagianni, D, Biswas, D, Levi, D, Larose Cadieux, E, Lim, E, Colliver, E, Nye, E, Galvez-Cancino, F, Gimeno-Valiente, F, Kassiotis, G, Stavrou, G, Mastrokalos, G, Lowe, H, Matos, I, Noorani, I, Goldman, J, Reading, J, Rane, J, Nicod, J, Hartley, J, Peggs, K, Enfield, K, Selvaraju, K, Thol, K, Ng, K, Chen, K, Dijkstra, K, Grigoriadis, K, Thakkar, K, Ensell, L, Shah, M, Litovchenko, M, Jamal-Hanjani, M, Werner Sunderland, M, Huska, M, Hill, M, Dietzen, M, Leung, M, Escudero, M, Tanic, M, Sivakumar, M, Chervova, O, Lucas, O, Pich, O, Al-Sawaf, O, Prymas, P, Hobson, P, Pawlik, P, Stone, R, Bentham, R, Vendramin, R, Saghafinia, S, Gamble, S, Veeriah, S, Ung, S, Quezada, S, Vanloo, S, Hessey, S, Ward, S, Harries, S, Boeing, S, Beck, S, Bola, S, Karasaki, T, Denner, T, Marafioti, T, Jones, T, Spanswick, V, Barbe, V, Lu, W, Liu, W, Wu, Y, Naito, Y, Ramsden, Z, Veiga, C, Royle, G, Collins-Fekete, C, Fraioli, F, Ashford, P, Forster, M, Lee, S, Borg, E, Falzon, M, Papadatos-Pastos, D, Wilson, J, Ahmad, T, Procter, A, Ahmed, A, Taylor, M, Nair, A, Lawrence, D, Patrini, D, Navani, N, Thakrar, R, Janes, S, Martinoni Hoogenboom, E, Monk, F, Holding, J, Choudhary, J, Bhakhri, K, Scarci, M, Gorman, P, Khiroya, R, Stephens, R, Wong, Y, Kaplar, Z, Bandula, S, Hackshaw, A, Hacker, A, Sharp, A, Smith, S, Kaur Dhanda, H, Pilotti, C, Leslie, R, Grapa, A, Zhang, H, Abduljabbar, K, Pan, X, Yuan, Y, Chuter, D, Mackenzie, M, Chee, S, Alzetani, A, Cave, J, Richards, J, De Sousa, P, Jordan, S, Rice, A, Raubenheimer, H, Bhayani, H, Ambrose, L, Devaraj, A, Chavan, H, Begum, S, Buderi, S, Kaniu, D, Malima, M, Booth, S, Nicholson, A, Fernandes, N, Shah, P, Proli, C, Hewish, M, Danson, S, Shackcloth, M, Robinson, L, Russell, P, Blyth, K, Kidd, A, Dick, C, Le Quesne, J, Kirk, A, Asif, M, Bilancia, R, Kostoulas, N, Thomas, M, Hynds, R, Kanu, N, Zaccaria, S, Gronroos, E, Swanton, C, Hobor S., Al Bakir M., Hiley C. T., Skrzypski M., Frankell A. M., Bakker B., Watkins T. B. K., Markovets A., Dry J. R., Brown A. P., van der Aart J., van den Bos H., Spierings D., Oukrif D., Novelli M., Chakrabarti T., Rabinowitz A. H., Ait Hassou L., Litiere S., Kerr D. L., Tan L., Kelly G., Moore D. A., Renshaw M. J., Venkatesan S., Hill W., Huebner A., Martinez-Ruiz C., Black J. R. M., Wu W., Angelova M., McGranahan N., Downward J., Chmielecki J., Barrett C., Litchfield K., Chew S. K., Blakely C. M., de Bruin E. C., Foijer F., Vousden K. H., Bivona T. G., Lester J. F., Bajaj A., Nakas A., Sodha-Ramdeen A., Tufail M., Scotland M., Boyles R., Rathinam S., Wilson C., Marrone D., Dulloo S., Fennell D. A., Matharu G., Shaw J. A., Boleti E., Cheyne H., Khalil M., Richardson S., Cruickshank T., Price G., Kerr K. M., Benafif S., French J., Gilbert K., Naidu B., Patel A. J., Osman A., Enstone C., Langman G., Shackleford H., Djearaman M., Kadiri S., Middleton G., Leek A., Hodgkinson J. D., Totton N., Montero A., Smith E., Fontaine E., Granato F., Paiva-Correia A., Novasio J., Rammohan K., Joseph L., Bishop P., Shah R., Moss S., Joshi V., Crosbie P. A. J., Brown K. D., Carter M., Chaturvedi A., Oliveira P., Lindsay C. R., Blackhall F. H., Krebs M. G., Summers Y., Clipson A., Tugwood J., Kerr A., Rothwell D. G., Dive C., Aerts H. J. W. L., Schwarz R. F., Kaufmann T. L., Wilson G. A., Rosenthal R., Van Loo P., Birkbak N. J., Szallasi Z., Kisistok J., Sokac M., Salgado R., Diossy M., Demeulemeester J., Bunkum A., Dwornik A., Magness A., Rowan A. J., Karamani A., Toncheva A., Chain B., Castignani C., Bailey C., Abbosh C., Puttick C., Weeden C. E., Lee C., Richard C., Naceur-Lombardelli C., Pearce D. R., Karagianni D., Biswas D., Levi D., Larose Cadieux E., Lim E. L., Colliver E., Nye E., Galvez-Cancino F., Gimeno-Valiente F., Kassiotis G., Stavrou G., Mastrokalos G. -T., Lowe H. L., Matos I. G., Noorani I., Goldman J., Reading J. L., Rane J. K., Nicod J., Hartley J. A., Peggs K. S., Enfield K. S. S., Selvaraju K., Thol K., Ng K. W., Chen K., Dijkstra K., Grigoriadis K., Thakkar K., Ensell L., Shah M., Litovchenko M., Jamal-Hanjani M., Werner Sunderland M., Huska M. R., Hill M. S., Dietzen M., Leung M. M., Escudero M., Tanic M., Sivakumar M., Chervova O., Lucas O., Pich O., Al-Sawaf O., Prymas P., Hobson P., Pawlik P., Stone R. K., Bentham R., Vendramin R., Saghafinia S., Gamble S., Veeriah S., Ung S. K. A., Quezada S. A., Vanloo S., Hessey S., Ward S., Harries S., Boeing S., Beck S., Bola S. K., Karasaki T., Denner T., Marafioti T., Jones T. P., Spanswick V., Barbe V., Lu W. -T., Liu W. K., Wu Y., Naito Y., Ramsden Z., Veiga C., Royle G., Collins-Fekete C. -A., Fraioli F., Ashford P., Forster M. D., Lee S. M., Borg E., Falzon M., Papadatos-Pastos D., Wilson J., Ahmad T., Procter A. J., Ahmed A., Taylor M. N., Nair A., Lawrence D., Patrini D., Navani N., Thakrar R. M., Janes S. M., Martinoni Hoogenboom E., Monk F., Holding J. W., Choudhary J., Bhakhri K., Scarci M., Gorman P., Khiroya R., Stephens R. C. M., Wong Y. N. S., Kaplar Z., Bandula S., Hackshaw A., Hacker A. -M., Sharp A., Smith S., Kaur Dhanda H., Pilotti C., Leslie R., Grapa A., Zhang H., AbdulJabbar K., Pan X., Yuan Y., Chuter D., MacKenzie M., Chee S., Alzetani A., Cave J., Richards J., Lim E., De Sousa P., Jordan S., Rice A., Raubenheimer H., Bhayani H., Ambrose L., Devaraj A., Chavan H., Begum S., Buderi S. I., Kaniu D., Malima M., Booth S., Nicholson A. G., Fernandes N., Shah P., Proli C., Hewish M., Danson S., Shackcloth M. J., Robinson L., Russell P., Blyth K. G., Kidd A., Dick C., Le Quesne J., Kirk A., Asif M., Bilancia R., Kostoulas N., Thomas M., Hynds R. E., Kanu N., Zaccaria S., Gronroos E., Swanton C., Hobor, S, Al Bakir, M, Hiley, C, Skrzypski, M, Frankell, A, Bakker, B, Watkins, T, Markovets, A, Dry, J, Brown, A, van der Aart, J, van den Bos, H, Spierings, D, Oukrif, D, Novelli, M, Chakrabarti, T, Rabinowitz, A, Ait Hassou, L, Litiere, S, Kerr, D, Tan, L, Kelly, G, Moore, D, Renshaw, M, Venkatesan, S, Hill, W, Huebner, A, Martinez-Ruiz, C, Black, J, Wu, W, Angelova, M, Mcgranahan, N, Downward, J, Chmielecki, J, Barrett, C, Litchfield, K, Chew, S, Blakely, C, de Bruin, E, Foijer, F, Vousden, K, Bivona, T, Lester, J, Bajaj, A, Nakas, A, Sodha-Ramdeen, A, Tufail, M, Scotland, M, Boyles, R, Rathinam, S, Wilson, C, Marrone, D, Dulloo, S, Fennell, D, Matharu, G, Shaw, J, Boleti, E, Cheyne, H, Khalil, M, Richardson, S, Cruickshank, T, Price, G, Kerr, K, Benafif, S, French, J, Gilbert, K, Naidu, B, Patel, A, Osman, A, Enstone, C, Langman, G, Shackleford, H, Djearaman, M, Kadiri, S, Middleton, G, Leek, A, Hodgkinson, J, Totton, N, Montero, A, Smith, E, Fontaine, E, Granato, F, Paiva-Correia, A, Novasio, J, Rammohan, K, Joseph, L, Bishop, P, Shah, R, Moss, S, Joshi, V, Crosbie, P, Brown, K, Carter, M, Chaturvedi, A, Oliveira, P, Lindsay, C, Blackhall, F, Krebs, M, Summers, Y, Clipson, A, Tugwood, J, Kerr, A, Rothwell, D, Dive, C, Aerts, H, Schwarz, R, Kaufmann, T, Wilson, G, Rosenthal, R, Van Loo, P, Birkbak, N, Szallasi, Z, Kisistok, J, Sokac, M, Salgado, R, Diossy, M, Demeulemeester, J, Bunkum, A, Dwornik, A, Magness, A, Rowan, A, Karamani, A, Toncheva, A, Chain, B, Castignani, C, Bailey, C, Abbosh, C, Puttick, C, Weeden, C, Lee, C, Richard, C, Naceur-Lombardelli, C, Pearce, D, Karagianni, D, Biswas, D, Levi, D, Larose Cadieux, E, Lim, E, Colliver, E, Nye, E, Galvez-Cancino, F, Gimeno-Valiente, F, Kassiotis, G, Stavrou, G, Mastrokalos, G, Lowe, H, Matos, I, Noorani, I, Goldman, J, Reading, J, Rane, J, Nicod, J, Hartley, J, Peggs, K, Enfield, K, Selvaraju, K, Thol, K, Ng, K, Chen, K, Dijkstra, K, Grigoriadis, K, Thakkar, K, Ensell, L, Shah, M, Litovchenko, M, Jamal-Hanjani, M, Werner Sunderland, M, Huska, M, Hill, M, Dietzen, M, Leung, M, Escudero, M, Tanic, M, Sivakumar, M, Chervova, O, Lucas, O, Pich, O, Al-Sawaf, O, Prymas, P, Hobson, P, Pawlik, P, Stone, R, Bentham, R, Vendramin, R, Saghafinia, S, Gamble, S, Veeriah, S, Ung, S, Quezada, S, Vanloo, S, Hessey, S, Ward, S, Harries, S, Boeing, S, Beck, S, Bola, S, Karasaki, T, Denner, T, Marafioti, T, Jones, T, Spanswick, V, Barbe, V, Lu, W, Liu, W, Wu, Y, Naito, Y, Ramsden, Z, Veiga, C, Royle, G, Collins-Fekete, C, Fraioli, F, Ashford, P, Forster, M, Lee, S, Borg, E, Falzon, M, Papadatos-Pastos, D, Wilson, J, Ahmad, T, Procter, A, Ahmed, A, Taylor, M, Nair, A, Lawrence, D, Patrini, D, Navani, N, Thakrar, R, Janes, S, Martinoni Hoogenboom, E, Monk, F, Holding, J, Choudhary, J, Bhakhri, K, Scarci, M, Gorman, P, Khiroya, R, Stephens, R, Wong, Y, Kaplar, Z, Bandula, S, Hackshaw, A, Hacker, A, Sharp, A, Smith, S, Kaur Dhanda, H, Pilotti, C, Leslie, R, Grapa, A, Zhang, H, Abduljabbar, K, Pan, X, Yuan, Y, Chuter, D, Mackenzie, M, Chee, S, Alzetani, A, Cave, J, Richards, J, De Sousa, P, Jordan, S, Rice, A, Raubenheimer, H, Bhayani, H, Ambrose, L, Devaraj, A, Chavan, H, Begum, S, Buderi, S, Kaniu, D, Malima, M, Booth, S, Nicholson, A, Fernandes, N, Shah, P, Proli, C, Hewish, M, Danson, S, Shackcloth, M, Robinson, L, Russell, P, Blyth, K, Kidd, A, Dick, C, Le Quesne, J, Kirk, A, Asif, M, Bilancia, R, Kostoulas, N, Thomas, M, Hynds, R, Kanu, N, Zaccaria, S, Gronroos, E, Swanton, C, Hobor S., Al Bakir M., Hiley C. T., Skrzypski M., Frankell A. M., Bakker B., Watkins T. B. K., Markovets A., Dry J. R., Brown A. P., van der Aart J., van den Bos H., Spierings D., Oukrif D., Novelli M., Chakrabarti T., Rabinowitz A. H., Ait Hassou L., Litiere S., Kerr D. L., Tan L., Kelly G., Moore D. A., Renshaw M. J., Venkatesan S., Hill W., Huebner A., Martinez-Ruiz C., Black J. R. M., Wu W., Angelova M., McGranahan N., Downward J., Chmielecki J., Barrett C., Litchfield K., Chew S. K., Blakely C. M., de Bruin E. C., Foijer F., Vousden K. H., Bivona T. G., Lester J. F., Bajaj A., Nakas A., Sodha-Ramdeen A., Tufail M., Scotland M., Boyles R., Rathinam S., Wilson C., Marrone D., Dulloo S., Fennell D. A., Matharu G., Shaw J. A., Boleti E., Cheyne H., Khalil M., Richardson S., Cruickshank T., Price G., Kerr K. M., Benafif S., French J., Gilbert K., Naidu B., Patel A. J., Osman A., Enstone C., Langman G., Shackleford H., Djearaman M., Kadiri S., Middleton G., Leek A., Hodgkinson J. D., Totton N., Montero A., Smith E., Fontaine E., Granato F., Paiva-Correia A., Novasio J., Rammohan K., Joseph L., Bishop P., Shah R., Moss S., Joshi V., Crosbie P. A. J., Brown K. D., Carter M., Chaturvedi A., Oliveira P., Lindsay C. R., Blackhall F. H., Krebs M. G., Summers Y., Clipson A., Tugwood J., Kerr A., Rothwell D. G., Dive C., Aerts H. J. W. L., Schwarz R. F., Kaufmann T. L., Wilson G. A., Rosenthal R., Van Loo P., Birkbak N. J., Szallasi Z., Kisistok J., Sokac M., Salgado R., Diossy M., Demeulemeester J., Bunkum A., Dwornik A., Magness A., Rowan A. J., Karamani A., Toncheva A., Chain B., Castignani C., Bailey C., Abbosh C., Puttick C., Weeden C. E., Lee C., Richard C., Naceur-Lombardelli C., Pearce D. R., Karagianni D., Biswas D., Levi D., Larose Cadieux E., Lim E. L., Colliver E., Nye E., Galvez-Cancino F., Gimeno-Valiente F., Kassiotis G., Stavrou G., Mastrokalos G. -T., Lowe H. L., Matos I. G., Noorani I., Goldman J., Reading J. L., Rane J. K., Nicod J., Hartley J. A., Peggs K. S., Enfield K. S. S., Selvaraju K., Thol K., Ng K. W., Chen K., Dijkstra K., Grigoriadis K., Thakkar K., Ensell L., Shah M., Litovchenko M., Jamal-Hanjani M., Werner Sunderland M., Huska M. R., Hill M. S., Dietzen M., Leung M. M., Escudero M., Tanic M., Sivakumar M., Chervova O., Lucas O., Pich O., Al-Sawaf O., Prymas P., Hobson P., Pawlik P., Stone R. K., Bentham R., Vendramin R., Saghafinia S., Gamble S., Veeriah S., Ung S. K. A., Quezada S. A., Vanloo S., Hessey S., Ward S., Harries S., Boeing S., Beck S., Bola S. K., Karasaki T., Denner T., Marafioti T., Jones T. P., Spanswick V., Barbe V., Lu W. -T., Liu W. K., Wu Y., Naito Y., Ramsden Z., Veiga C., Royle G., Collins-Fekete C. -A., Fraioli F., Ashford P., Forster M. D., Lee S. M., Borg E., Falzon M., Papadatos-Pastos D., Wilson J., Ahmad T., Procter A. J., Ahmed A., Taylor M. N., Nair A., Lawrence D., Patrini D., Navani N., Thakrar R. M., Janes S. M., Martinoni Hoogenboom E., Monk F., Holding J. W., Choudhary J., Bhakhri K., Scarci M., Gorman P., Khiroya R., Stephens R. C. M., Wong Y. N. S., Kaplar Z., Bandula S., Hackshaw A., Hacker A. -M., Sharp A., Smith S., Kaur Dhanda H., Pilotti C., Leslie R., Grapa A., Zhang H., AbdulJabbar K., Pan X., Yuan Y., Chuter D., MacKenzie M., Chee S., Alzetani A., Cave J., Richards J., Lim E., De Sousa P., Jordan S., Rice A., Raubenheimer H., Bhayani H., Ambrose L., Devaraj A., Chavan H., Begum S., Buderi S. I., Kaniu D., Malima M., Booth S., Nicholson A. G., Fernandes N., Shah P., Proli C., Hewish M., Danson S., Shackcloth M. J., Robinson L., Russell P., Blyth K. G., Kidd A., Dick C., Le Quesne J., Kirk A., Asif M., Bilancia R., Kostoulas N., Thomas M., Hynds R. E., Kanu N., Zaccaria S., Gronroos E., and Swanton C.
Abstract: The phenomenon of mixed/heterogenous treatment responses to cancer therapies within an individual patient presents a challenging clinical scenario. Furthermore, the molecular basis of mixed intra-patient tumor responses remains unclear. Here, we show that patients with metastatic lung adenocarcinoma harbouring co-mutations of EGFR and TP53, are more likely to have mixed intra-patient tumor responses to EGFR tyrosine kinase inhibition (TKI), compared to those with an EGFR mutation alone. The combined presence of whole genome doubling (WGD) and TP53 co-mutations leads to increased genome instability and genomic copy number aberrations in genes implicated in EGFR TKI resistance. Using mouse models and an in vitro isogenic p53-mutant model system, we provide evidence that WGD provides diverse routes to drug resistance by increasing the probability of acquiring copy-number gains or losses relative to non-WGD cells. These data provide a molecular basis for mixed tumor responses to targeted therapy, within an individual patient, with implications for therapeutic strategies.
Published: 2024

2. The artificial intelligence-based model ANORAK improves histopathological grading of lung adenocarcinoma

Author: Pan, X, Abduljabbar, K, Coelho-Lima, J, Grapa, A, Zhang, H, Cheung, A, Baena, J, Karasaki, T, Wilson, C, Sereno, M, Veeriah, S, Aitken, S, Hackshaw, A, Nicholson, A, Jamal-Hanjani, M, Le Quesne, J, Janes, S, Hacker, A, Sharp, A, Smith, S, Dhanda, H, Chan, K, Pilotti, C, Leslie, R, Chuter, D, Mackenzie, M, Chee, S, Alzetani, A, Lim, E, De Sousa, P, Jordan, S, Rice, A, Raubenheimer, H, Bhayani, H, Ambrose, L, Devaraj, A, Chavan, H, Begum, S, Buderi, S, Kaniu, D, Malima, M, Booth, S, Fernandes, N, Shah, P, Proli, C, Hewish, M, Danson, S, Shackcloth, M, Robinson, L, Russell, P, Blyth, K, Kidd, A, Kirk, A, Asif, M, Bilancia, R, Kostoulas, N, Thomas, M, Dick, C, Lester, J, Bajaj, A, Nakas, A, Sodha-Ramdeen, A, Tufail, M, Scotland, M, Boyles, R, Rathinam, S, Fennell, D, Marrone, D, Dulloo, S, Matharu, G, Shaw, J, Riley, J, Primrose, L, Boleti, E, Cheyne, H, Khalil, M, Richardson, S, Cruickshank, T, Price, G, Kerr, K, Benafif, S, Papadatos-Pastos, D, Wilson, J, Ahmad, T, French, J, Gilbert, K, Naidu, B, Patel, A, Osman, A, Lacson, C, Langman, G, Shackleford, H, Djearaman, M, Kadiri, S, Middleton, G, Leek, A, Hodgkinson, J, Totten, N, Montero, A, Smith, E, Fontaine, E, Granato, F, Novasio, J, Rammohan, K, Joseph, L, Bishop, P, Shah, R, Moss, S, Joshi, V, Crosbie, P, Paiva-Correia, A, Chaturvedi, A, Priest, L, Oliveira, P, Gomes, F, Brown, K, Carter, M, Lindsay, C, Blackhall, F, Krebs, M, Summers, Y, Clipson, A, Tugwood, J, Kerr, A, Rothwell, D, Dive, C, Aerts, H, Schwarz, R, Kaufmann, T, Van Loo, P, Wilson, G, Rosenthal, R, Rowan, A, Bailey, C, Lee, C, Colliver, E, Enfield, K, Hill, M, Angelova, M, Pich, O, Leung, M, Frankell, A, Hiley, C, Zhai, H, Bakir, M, Birkbak, N, Lucas, O, Huebner, A, Puttick, C, Grigoriadis, K, Dietzen, M, Biswas, D, Athanasopoulou, F, Ward, S, Demeulemeester, J, Castignani, C, Cadieux, E, Kisistok, J, Sokac, M, Szallasi, Z, Diossy, M, Salgado, R, Stewart, A, Magness, A, Weeden, C, Levi, D, Gronroos, E, Noorani, I, Goldman, J, Escudero, M, Hobson, P, Vendramin, R, Boeing, S, Denner, T, Barbe, V, Lu, W, Hill, W, Naito, Y, Ramsden, Z, Kassiotis, G, Dwornik, A, Karamani, A, Chain, B, Pearce, D, Karagianni, D, Galvez-Cancino, F, Stavrou, G, Mastrokalos, G, Lowe, H, Matos, I, Reading, J, Hartley, J, Selvaraju, K, Chen, K, Ensell, L, Shah, M, Litovchenko, M, Chervova, O, Pawlik, P, Hynds, R, Gamble, S, Ung, S, Bola, S, Spanswick, V, Wu, Y, Al-Sawaf, O, Jones, T, Beck, S, Tanic, M, Marafioti, T, Borg, E, Falzon, M, Khiroya, R, Toncheva, A, Abbosh, C, Richard, C, Naceur-Lombardelli, C, Gimeno-Valiente, F, Thakkar, K, Sunderland, M, Sivakumar, M, Kanu, N, Prymas, P, Saghafinia, S, Vanloo, S, Lam, J, Liu, W, Bunkum, A, Hessey, S, Zaccaria, S, Martinez-Ruiz, C, Black, J, Thol, K, Bentham, R, Litchfield, K, Mcgranahan, N, Quezada, S, Forster, M, Lee, S, Herrero, J, Nye, E, Stone, R, Nicod, J, Rane, J, Peggs, K, Ng, K, Dijkstra, K, Huska, M, Hoogenboom, E, Monk, F, Holding, J, Choudhary, J, Bhakhri, K, Scarci, M, Gorman, P, Stephens, R, Wong, Y, Kaplar, Z, Bandula, S, Watkins, T, Veiga, C, Royle, G, Collins-Fekete, C, Fraioli, F, Ashford, P, Procter, A, Ahmed, A, Taylor, M, Nair, A, Lawrence, D, Patrini, D, Navani, N, Thakrar, R, Swanton, C, Yuan, Y, Moore, D, Pan X., AbdulJabbar K., Coelho-Lima J., Grapa A. -I., Zhang H., Cheung A. H. K., Baena J., Karasaki T., Wilson C. R., Sereno M., Veeriah S., Aitken S. J., Hackshaw A., Nicholson A. G., Jamal-Hanjani M., Le Quesne J., Janes S. M., Hacker A. -M., Sharp A., Smith S., Dhanda H. K., Chan K., Pilotti C., Leslie R., Chuter D., MacKenzie M., Chee S., Alzetani A., Lim E., De Sousa P., Jordan S., Rice A., Raubenheimer H., Bhayani H., Ambrose L., Devaraj A., Chavan H., Begum S., Buderi S. I., Kaniu D., Malima M., Booth S., Fernandes N., Shah P., Proli C., Hewish M., Danson S., Shackcloth M. J., Robinson L., Russell P., Blyth K. G., Kidd A., Kirk A., Asif M., Bilancia R., Kostoulas N., Thomas M., Dick C., Lester J. F., Bajaj A., Nakas A., Sodha-Ramdeen A., Tufail M., Scotland M., Boyles R., Rathinam S., Fennell D. A., Wilson C., Marrone D., Dulloo S., Matharu G., Shaw J. A., Riley J., Primrose L., Boleti E., Cheyne H., Khalil M., Richardson S., Cruickshank T., Price G., Kerr K. M., Benafif S., Papadatos-Pastos D., Wilson J., Ahmad T., French J., Gilbert K., Naidu B., Patel A. J., Osman A., Lacson C., Langman G., Shackleford H., Djearaman M., Kadiri S., Middleton G., Leek A., Hodgkinson J. D., Totten N., Montero A., Smith E., Fontaine E., Granato F., Novasio J., Rammohan K., Joseph L., Bishop P., Shah R., Moss S., Joshi V., Crosbie P., Paiva-Correia A., Chaturvedi A., Priest L., Oliveira P., Gomes F., Brown K., Carter M., Lindsay C. R., Blackhall F. H., Krebs M. G., Summers Y., Clipson A., Tugwood J., Kerr A., Rothwell D. G., Dive C., Aerts H. J. W. L., Schwarz R. F., Kaufmann T. L., Van Loo P., Wilson G. A., Rosenthal R., Rowan A., Bailey C., Lee C., Colliver E., Enfield K. S. S., Hill M. S., Angelova M., Pich O., Leung M., Frankell A. M., Hiley C. T., Lim E. L., Zhai H., Bakir M. A., Birkbak N. J., Lucas O., Huebner A., Puttick C., Grigoriadis K., Dietzen M., Biswas D., Athanasopoulou F., Ward S., Demeulemeester J., Castignani C., Cadieux E. L., Kisistok J., Sokac M., Szallasi Z., Diossy M., Salgado R., Stewart A., Magness A., Weeden C. E., Levi D., Gronroos E., Noorani I., Goldman J., Escudero M., Hobson P., Vendramin R., Boeing S., Denner T., Barbe V., Lu W. -T., Hill W., Naito Y., Ramsden Z., Kassiotis G., Dwornik A., Karamani A., Chain B., Pearce D. R., Karagianni D., Galvez-Cancino F., Stavrou G., Mastrokalos G., Lowe H. L., Matos I. G., Reading J. L., Hartley J. A., Selvaraju K., Chen K., Ensell L., Shah M., Litovchenko M., Chervova O., Pawlik P., Hynds R. E., Gamble S., Ung S. K. A., Bola S. K., Spanswick V., Wu Y., Al-Sawaf O., Jones T. P., Beck S., Tanic M., Marafioti T., Borg E., Falzon M., Khiroya R., Toncheva A., Abbosh C., Richard C., Naceur-Lombardelli C., Gimeno-Valiente F., Thakkar K., Sunderland M. W., Sivakumar M., Kanu N., Prymas P., Saghafinia S., Vanloo S., Lam J. M., Liu W. K., Bunkum A., Hessey S., Zaccaria S., Martinez-Ruiz C., Black J. R. M., Thol K., Bentham R., Litchfield K., McGranahan N., Quezada S. A., Forster M. D., Lee S. M., Herrero J., Nye E., Stone R. K., Nicod J., Rane J. K., Peggs K. S., Ng K. W., Dijkstra K., Huska M. R., Hoogenboom E. M., Monk F., Holding J. W., Choudhary J., Bhakhri K., Scarci M., Gorman P., Stephens R. C. M., Wong Y. N. S., Kaplar Z., Bandula S., Watkins T. B. K., Veiga C., Royle G., Collins-Fekete C. -A., Fraioli F., Ashford P., Procter A. J., Ahmed A., Taylor M. N., Nair A., Lawrence D., Patrini D., Navani N., Thakrar R. M., Swanton C., Yuan Y., Moore D. A., Pan, X, Abduljabbar, K, Coelho-Lima, J, Grapa, A, Zhang, H, Cheung, A, Baena, J, Karasaki, T, Wilson, C, Sereno, M, Veeriah, S, Aitken, S, Hackshaw, A, Nicholson, A, Jamal-Hanjani, M, Le Quesne, J, Janes, S, Hacker, A, Sharp, A, Smith, S, Dhanda, H, Chan, K, Pilotti, C, Leslie, R, Chuter, D, Mackenzie, M, Chee, S, Alzetani, A, Lim, E, De Sousa, P, Jordan, S, Rice, A, Raubenheimer, H, Bhayani, H, Ambrose, L, Devaraj, A, Chavan, H, Begum, S, Buderi, S, Kaniu, D, Malima, M, Booth, S, Fernandes, N, Shah, P, Proli, C, Hewish, M, Danson, S, Shackcloth, M, Robinson, L, Russell, P, Blyth, K, Kidd, A, Kirk, A, Asif, M, Bilancia, R, Kostoulas, N, Thomas, M, Dick, C, Lester, J, Bajaj, A, Nakas, A, Sodha-Ramdeen, A, Tufail, M, Scotland, M, Boyles, R, Rathinam, S, Fennell, D, Marrone, D, Dulloo, S, Matharu, G, Shaw, J, Riley, J, Primrose, L, Boleti, E, Cheyne, H, Khalil, M, Richardson, S, Cruickshank, T, Price, G, Kerr, K, Benafif, S, Papadatos-Pastos, D, Wilson, J, Ahmad, T, French, J, Gilbert, K, Naidu, B, Patel, A, Osman, A, Lacson, C, Langman, G, Shackleford, H, Djearaman, M, Kadiri, S, Middleton, G, Leek, A, Hodgkinson, J, Totten, N, Montero, A, Smith, E, Fontaine, E, Granato, F, Novasio, J, Rammohan, K, Joseph, L, Bishop, P, Shah, R, Moss, S, Joshi, V, Crosbie, P, Paiva-Correia, A, Chaturvedi, A, Priest, L, Oliveira, P, Gomes, F, Brown, K, Carter, M, Lindsay, C, Blackhall, F, Krebs, M, Summers, Y, Clipson, A, Tugwood, J, Kerr, A, Rothwell, D, Dive, C, Aerts, H, Schwarz, R, Kaufmann, T, Van Loo, P, Wilson, G, Rosenthal, R, Rowan, A, Bailey, C, Lee, C, Colliver, E, Enfield, K, Hill, M, Angelova, M, Pich, O, Leung, M, Frankell, A, Hiley, C, Zhai, H, Bakir, M, Birkbak, N, Lucas, O, Huebner, A, Puttick, C, Grigoriadis, K, Dietzen, M, Biswas, D, Athanasopoulou, F, Ward, S, Demeulemeester, J, Castignani, C, Cadieux, E, Kisistok, J, Sokac, M, Szallasi, Z, Diossy, M, Salgado, R, Stewart, A, Magness, A, Weeden, C, Levi, D, Gronroos, E, Noorani, I, Goldman, J, Escudero, M, Hobson, P, Vendramin, R, Boeing, S, Denner, T, Barbe, V, Lu, W, Hill, W, Naito, Y, Ramsden, Z, Kassiotis, G, Dwornik, A, Karamani, A, Chain, B, Pearce, D, Karagianni, D, Galvez-Cancino, F, Stavrou, G, Mastrokalos, G, Lowe, H, Matos, I, Reading, J, Hartley, J, Selvaraju, K, Chen, K, Ensell, L, Shah, M, Litovchenko, M, Chervova, O, Pawlik, P, Hynds, R, Gamble, S, Ung, S, Bola, S, Spanswick, V, Wu, Y, Al-Sawaf, O, Jones, T, Beck, S, Tanic, M, Marafioti, T, Borg, E, Falzon, M, Khiroya, R, Toncheva, A, Abbosh, C, Richard, C, Naceur-Lombardelli, C, Gimeno-Valiente, F, Thakkar, K, Sunderland, M, Sivakumar, M, Kanu, N, Prymas, P, Saghafinia, S, Vanloo, S, Lam, J, Liu, W, Bunkum, A, Hessey, S, Zaccaria, S, Martinez-Ruiz, C, Black, J, Thol, K, Bentham, R, Litchfield, K, Mcgranahan, N, Quezada, S, Forster, M, Lee, S, Herrero, J, Nye, E, Stone, R, Nicod, J, Rane, J, Peggs, K, Ng, K, Dijkstra, K, Huska, M, Hoogenboom, E, Monk, F, Holding, J, Choudhary, J, Bhakhri, K, Scarci, M, Gorman, P, Stephens, R, Wong, Y, Kaplar, Z, Bandula, S, Watkins, T, Veiga, C, Royle, G, Collins-Fekete, C, Fraioli, F, Ashford, P, Procter, A, Ahmed, A, Taylor, M, Nair, A, Lawrence, D, Patrini, D, Navani, N, Thakrar, R, Swanton, C, Yuan, Y, Moore, D, Pan X., AbdulJabbar K., Coelho-Lima J., Grapa A. -I., Zhang H., Cheung A. H. K., Baena J., Karasaki T., Wilson C. R., Sereno M., Veeriah S., Aitken S. J., Hackshaw A., Nicholson A. G., Jamal-Hanjani M., Le Quesne J., Janes S. M., Hacker A. -M., Sharp A., Smith S., Dhanda H. K., Chan K., Pilotti C., Leslie R., Chuter D., MacKenzie M., Chee S., Alzetani A., Lim E., De Sousa P., Jordan S., Rice A., Raubenheimer H., Bhayani H., Ambrose L., Devaraj A., Chavan H., Begum S., Buderi S. I., Kaniu D., Malima M., Booth S., Fernandes N., Shah P., Proli C., Hewish M., Danson S., Shackcloth M. J., Robinson L., Russell P., Blyth K. G., Kidd A., Kirk A., Asif M., Bilancia R., Kostoulas N., Thomas M., Dick C., Lester J. F., Bajaj A., Nakas A., Sodha-Ramdeen A., Tufail M., Scotland M., Boyles R., Rathinam S., Fennell D. A., Wilson C., Marrone D., Dulloo S., Matharu G., Shaw J. A., Riley J., Primrose L., Boleti E., Cheyne H., Khalil M., Richardson S., Cruickshank T., Price G., Kerr K. M., Benafif S., Papadatos-Pastos D., Wilson J., Ahmad T., French J., Gilbert K., Naidu B., Patel A. J., Osman A., Lacson C., Langman G., Shackleford H., Djearaman M., Kadiri S., Middleton G., Leek A., Hodgkinson J. D., Totten N., Montero A., Smith E., Fontaine E., Granato F., Novasio J., Rammohan K., Joseph L., Bishop P., Shah R., Moss S., Joshi V., Crosbie P., Paiva-Correia A., Chaturvedi A., Priest L., Oliveira P., Gomes F., Brown K., Carter M., Lindsay C. R., Blackhall F. H., Krebs M. G., Summers Y., Clipson A., Tugwood J., Kerr A., Rothwell D. G., Dive C., Aerts H. J. W. L., Schwarz R. F., Kaufmann T. L., Van Loo P., Wilson G. A., Rosenthal R., Rowan A., Bailey C., Lee C., Colliver E., Enfield K. S. S., Hill M. S., Angelova M., Pich O., Leung M., Frankell A. M., Hiley C. T., Lim E. L., Zhai H., Bakir M. A., Birkbak N. J., Lucas O., Huebner A., Puttick C., Grigoriadis K., Dietzen M., Biswas D., Athanasopoulou F., Ward S., Demeulemeester J., Castignani C., Cadieux E. L., Kisistok J., Sokac M., Szallasi Z., Diossy M., Salgado R., Stewart A., Magness A., Weeden C. E., Levi D., Gronroos E., Noorani I., Goldman J., Escudero M., Hobson P., Vendramin R., Boeing S., Denner T., Barbe V., Lu W. -T., Hill W., Naito Y., Ramsden Z., Kassiotis G., Dwornik A., Karamani A., Chain B., Pearce D. R., Karagianni D., Galvez-Cancino F., Stavrou G., Mastrokalos G., Lowe H. L., Matos I. G., Reading J. L., Hartley J. A., Selvaraju K., Chen K., Ensell L., Shah M., Litovchenko M., Chervova O., Pawlik P., Hynds R. E., Gamble S., Ung S. K. A., Bola S. K., Spanswick V., Wu Y., Al-Sawaf O., Jones T. P., Beck S., Tanic M., Marafioti T., Borg E., Falzon M., Khiroya R., Toncheva A., Abbosh C., Richard C., Naceur-Lombardelli C., Gimeno-Valiente F., Thakkar K., Sunderland M. W., Sivakumar M., Kanu N., Prymas P., Saghafinia S., Vanloo S., Lam J. M., Liu W. K., Bunkum A., Hessey S., Zaccaria S., Martinez-Ruiz C., Black J. R. M., Thol K., Bentham R., Litchfield K., McGranahan N., Quezada S. A., Forster M. D., Lee S. M., Herrero J., Nye E., Stone R. K., Nicod J., Rane J. K., Peggs K. S., Ng K. W., Dijkstra K., Huska M. R., Hoogenboom E. M., Monk F., Holding J. W., Choudhary J., Bhakhri K., Scarci M., Gorman P., Stephens R. C. M., Wong Y. N. S., Kaplar Z., Bandula S., Watkins T. B. K., Veiga C., Royle G., Collins-Fekete C. -A., Fraioli F., Ashford P., Procter A. J., Ahmed A., Taylor M. N., Nair A., Lawrence D., Patrini D., Navani N., Thakrar R. M., Swanton C., Yuan Y., and Moore D. A.
Abstract: The introduction of the International Association for the Study of Lung Cancer grading system has furthered interest in histopathological grading for risk stratification in lung adenocarcinoma. Complex morphology and high intratumoral heterogeneity present challenges to pathologists, prompting the development of artificial intelligence (AI) methods. Here we developed ANORAK (pyrAmid pooliNg crOss stReam Attention networK), encoding multiresolution inputs with an attention mechanism, to delineate growth patterns from hematoxylin and eosin-stained slides. In 1,372 lung adenocarcinomas across four independent cohorts, AI-based grading was prognostic of disease-free survival, and further assisted pathologists by consistently improving prognostication in stage I tumors. Tumors with discrepant patterns between AI and pathologists had notably higher intratumoral heterogeneity. Furthermore, ANORAK facilitates the morphological and spatial assessment of the acinar pattern, capturing acinus variations with pattern transition. Collectively, our AI method enabled the precision quantification and morphology investigation of growth patterns, reflecting intratumoral histological transitions in lung adenocarcinoma.
Published: 2024

3. Investigation of turbulent flow over irregular rough surfaces using direct numerical simulations

Author: Thakkar, Manan and Sandham, Neil
Subjects: 532
Abstract: Incompressible turbulent flow in irregular rough channels is investigated using a finite-difference direct numerical simulation code which includes an iterative embedded boundary treatment to resolve the roughness. Seventeen industrially relevant rough surfaces with a wide variation in surface topography are considered. Various studies are conducted to understand the flow physics and the relationship between key flow parameters and surface topography. Studies at low values of friction Reynolds number, Reτ, for a single surface, show that the flow is laminar up to Reτ = 89 and begins to develop quasi-periodic fluctuations at Reτ = 89.5. Fluctuations in the three velocity components continue to grow until Reτ = 91, and the flow is turbulent for Reτ ≥ 92. Transition depends on the surface topography as some roughness peaks trigger fluctuations before others. For all the surfaces, mean and turbulent flow statistics are computed at Reτ = 180, for which the flow is fully turbulent but transitionally rough. All surfaces are scaled to the same physical roughness height. Nevertheless, a wide range of roughness function, ∆U+, values is obtained, indicating that it depends not only on the roughness height but also on the detailed roughness topography. Other mean and turbulence flow statistics also vary considerably depending on the surface topography. Next, based on the simulation results database at Reτ = 180, a newly formulated method, that determines which surface topographical properties are important and how new properties can be added to an empirical model, is tested. Optimised models with several roughness parameters are systematically developed for ∆U+ and profile peak turbulent kinetic energy. In determining ∆U+, besides the known parameters of solidity and skewness, it is shown that the streamwise correlation length and rms roughness height are also significant. The peak turbulent kinetic energy is determined by the skewness and rms roughness height, along with the mean forward-facing surface angle and spanwise effective slope. A Reynolds number dependence study is conducted for a single surface, wherein the roughness height in viscous units, k+, is varied from the transitionally rough to the fully-rough regime in the range 3.75 ≤ k+ ≤ 120. Excellent agreement with the experimental data of Nikuradse (Laws of flow in rough pipes, NACA Technical Memorandum 1292, 1933) is observed. The value of equivalent sand-grain roughness height, k+s,eq, thus obtained is close to the mean peak-to-valley height.
Published: 2017

4. Flexible and Biocompatible Antifouling Polyurethane Surfaces Incorporating Tethered Antimicrobial Peptides through Click Reactions

Author: Berglin, Mattias, Cavanagh, Jorunn Pauline, Caous, Josefin Seth, Thakkar, Balmukund Sureshkumar, Vasquez, Jeddah Marie, Stensen, Wenche, Lyvén, Benny, Svendsen, John-Sigurd, Svenson, Johan, Berglin, Mattias, Cavanagh, Jorunn Pauline, Caous, Josefin Seth, Thakkar, Balmukund Sureshkumar, Vasquez, Jeddah Marie, Stensen, Wenche, Lyvén, Benny, Svendsen, John-Sigurd, and Svenson, Johan
Abstract: Efficient, simple antibacterial materials to combat implant-associated infections are much in demand. Herein, the development of polyurethanes, both cross-linked thermoset and flexible and versatile thermoplastic, suitable for “click on demand” attachment of antibacterial compounds enabled via incorporation of an alkyne-containing diol monomer in the polymer backbone, is described. By employing different polyolic polytetrahydrofurans, isocyanates, and chain extenders, a robust and flexible material comparable to commercial thermoplastic polyurethane is prepared. A series of short synthetic antimicrobial peptides are designed, synthesized, and covalently attached in a single coupling step to generate a homogenous coating. The lead material is shown to be biocompatible and does not display any toxicity against either mouse fibroblasts or reconstructed human epidermis according to ISO and OECD guidelines. The repelling performance of the peptide-coated materials is illustrated against colonization and biofilm formation by Staphylococcus aureus and Staphylococcus epidermidis on coated plastic films and finally, on coated commercial central venous catheters employing LIVE/DEAD staining, confocal laser scanning microscopy, and bacterial counts. This study presents the successful development of a versatile and scalable polyurethane with the potential for use in the medical field to reduce the impact of bacterial biofilms., This study was financed by Amicoat A/S. The authors are grateful for the analytical assistance from RISE scientists L. Brive, P. Borchardt, K. Johansson, and J. Somertune.
Published: 2024
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5. Association Between Coronary Assessment in Heart Failure and Clinical Outcomes Within a Safety-Net Setting Using a Target Trial Emulation Observational Design

Author: Durstenfeld, Matthew S, Durstenfeld, Matthew S, Thakkar, Anjali, Ma, Yifei, Zier, Lucas S, Davis, Jonathan D, Hsue, Priscilla Y, Durstenfeld, Matthew S, Durstenfeld, Matthew S, Thakkar, Anjali, Ma, Yifei, Zier, Lucas S, Davis, Jonathan D, and Hsue, Priscilla Y
Abstract: BackgroundIschemic cardiomyopathy is the leading cause of heart failure (HF). Most patients do not undergo coronary assessment after HF diagnosis. There are no randomized clinical trials of coronary assessment after HF diagnosis.MethodsUsing an electronic health record cohort of all individuals with HF within the San Francisco Health Network from 2001 to 2019, we identified factors associated with coronary assessment. Then, we studied the association of coronary assessment within 30 days of HF diagnosis with all-cause mortality and a composite of mortality and emergent angiography using a target trial emulation observational comparative-effectiveness approach. Target trial emulation is an approach to causal inference based on creating a hypothetical randomized clinical trial protocol and using observational data to emulate the protocol. We used propensity scores for covariate adjustment. We used national death records to improve the ascertainment of mortality and included falsification end points for the cause of death.ResultsAmong 14 829 individuals with HF (median, 62 years old; 5855 [40%] women), 3987 (26.9%) ever completed coronary assessment, with 2467/13 301 (18.5%) with unknown coronary artery disease status at HF diagnosis assessed. Women, older individuals, and people without stable housing were less likely to complete coronary assessment. Among 5972 eligible persons of whom 627 underwent early elective coronary assessment, coronary assessment was associated with lower mortality (hazard ratio, 0.84 [95% CI, 0.72-0.97]; P=0.025), reduced risk of the composite outcome (hazard ratio, 0.86 [95% CI, 0.73-1.00]), higher rates of revascularization (odds ratio, 7.6 [95% CI, 5.4-10.6]), and higher use of medical therapy (odds ratio, 2.5 [95% CI, 1.7-3.6]), but not the falsification end points.ConclusionsIn a safety-net population, disparities in coronary assessment after HF diagnosis are not fully explained by coronary artery disease risk factors. Early coronary ass
Published: 2024

6. Pathological complete response in patients with resected pancreatic adenocarcinoma after preoperative chemotherapy

Author: Stoop, Thomas F., Oba, Atsushi, Wu, Y H Andrew, Beaty, Laurel E., Colborn, Kathryn L., Janssen, Boris V., Al-Musawi, Mohammed H., Franco, Salvador Rodriguez, Sugawara, Toshitaka, Franklin, Oskar, Jain, Ajay, Saiura, Akio, Sauvanet, Alain, Coppola, Alessandro, Javed, Ammar A., Groot Koerkamp, Bas, Miller, Braden N., Mack, Claudia E., Hashimoto, Daisuke, Caputo, Damiano, Kleive, Dyre, Sereni, Elisabetta, Belfiori, Giulio, Ichida, Hirofumi, van Dam, Jacob L., Dembinski, Jeanne, Akahoshi, Keiichi, Roberts, Keith J., Tanaka, Kimitaka, Labori, Knut J., Falconi, Massimo, House, Michael G., Sugimoto, Motokazu, Tanabe, Minoru, Gotohda, Naoto, Krohn, Paul S., Burkhart, Richard A., Thakkar, Rohan G., Pande, Rupaly, Dokmak, Safi, Hirano, Satoshi, Burgdorf, Stefan K., Crippa, Stefano, van Roessel, Stijn, Satoi, Sohei, White, Steven A., Hackert, Thilo, Nguyen, Trang K., Yamamoto, Tomohisa, Nakamura, Toru, Bachu, Vismaya, Burns, William R., Inoue, Yosuke, Takahashi, Yu, Ushida, Yuta, Aslami, Zohra V., Verbeke, Caroline S., Fariña, Arantza, He, Jin, Wilmink, Johanna W., Messersmith, Wells, Verheij, Joanne, Kaplan, Jeffrey, Schulick, Richard D., Besselink, Marc G., Del Chiaro, Marco, Stoop, Thomas F., Oba, Atsushi, Wu, Y H Andrew, Beaty, Laurel E., Colborn, Kathryn L., Janssen, Boris V., Al-Musawi, Mohammed H., Franco, Salvador Rodriguez, Sugawara, Toshitaka, Franklin, Oskar, Jain, Ajay, Saiura, Akio, Sauvanet, Alain, Coppola, Alessandro, Javed, Ammar A., Groot Koerkamp, Bas, Miller, Braden N., Mack, Claudia E., Hashimoto, Daisuke, Caputo, Damiano, Kleive, Dyre, Sereni, Elisabetta, Belfiori, Giulio, Ichida, Hirofumi, van Dam, Jacob L., Dembinski, Jeanne, Akahoshi, Keiichi, Roberts, Keith J., Tanaka, Kimitaka, Labori, Knut J., Falconi, Massimo, House, Michael G., Sugimoto, Motokazu, Tanabe, Minoru, Gotohda, Naoto, Krohn, Paul S., Burkhart, Richard A., Thakkar, Rohan G., Pande, Rupaly, Dokmak, Safi, Hirano, Satoshi, Burgdorf, Stefan K., Crippa, Stefano, van Roessel, Stijn, Satoi, Sohei, White, Steven A., Hackert, Thilo, Nguyen, Trang K., Yamamoto, Tomohisa, Nakamura, Toru, Bachu, Vismaya, Burns, William R., Inoue, Yosuke, Takahashi, Yu, Ushida, Yuta, Aslami, Zohra V., Verbeke, Caroline S., Fariña, Arantza, He, Jin, Wilmink, Johanna W., Messersmith, Wells, Verheij, Joanne, Kaplan, Jeffrey, Schulick, Richard D., Besselink, Marc G., and Del Chiaro, Marco
Abstract: Importance: Preoperative chemo(radio)therapy is increasingly used in patients with localized pancreatic adenocarcinoma, leading to pathological complete response (pCR) in a small subset of patients. However, multicenter studies with in-depth data about pCR are lacking. Objective: To investigate the incidence, outcome, and risk factors of pCR after preoperative chemo(radio)therapy. Design, Setting, and Participants: This observational, international, multicenter cohort study assessed all consecutive patients with pathology-proven localized pancreatic adenocarcinoma who underwent resection after 2 or more cycles of chemotherapy (with or without radiotherapy) in 19 centers from 8 countries (January 1, 2010, to December 31, 2018). Data collection was performed from February 1, 2020, to April 30, 2022, and analyses from January 1, 2022, to December 31, 2023. Median follow-up was 19 months. Exposures: Preoperative chemotherapy (with or without radiotherapy) followed by resection. Main Outcomes and Measures: The incidence of pCR (defined as absence of vital tumor cells in the sampled pancreas specimen after resection), its association with OS from surgery, and factors associated with pCR. Factors associated with overall survival (OS) and pCR were investigated with Cox proportional hazards and logistic regression models, respectively. Results: Overall, 1758 patients (mean [SD] age, 64 [9] years; 879 [50.0%] male) were studied. The rate of pCR was 4.8% (n = 85), and pCR was associated with OS (hazard ratio, 0.46; 95% CI, 0.26-0.83). The 1-, 3-, and 5-year OS rates were 95%, 82%, and 63% in patients with pCR vs 80%, 46%, and 30% in patients without pCR, respectively (P < .001). Factors associated with pCR included preoperative multiagent chemotherapy other than (m)FOLFIRINOX ([modified] leucovorin calcium [folinic acid], fluorouracil, irinotecan hydrochloride, and oxaliplatin) (odds ratio [OR], 0.48; 95% CI, 0.26-0.87), preoperative conventional radiotherapy (OR, 2.03; 95%
Published: 2024
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7. Integration of Machine Learning Algorithms with Cloud Computing for Real-Time Data Analysis

Author: Kanchetti, Devidas, Munirathnam, Rajesh, Thakkar, Darshit, Kanchetti, Devidas, Munirathnam, Rajesh, and Thakkar, Darshit
Abstract: As part of this study though, real-time data analysis is examined by exploring the combination of machine learning algorithms with cloud computing. It does so by defining optimization problems and solutions, as well as outlining optimization goals and directions for development. The efficiency of real time data processing ability is also amplified with the use of an amalgamation of machine learning and cloud computing though traditional systems are often associated with high failure rates and high costs of maintenance. Enhanced indexing, systematic control of information storage and retrieval, query optimization are the main benefits obtainable from this. This is because despite the challenges such as limited resources, integration has never been a problem even with challenges of data privacy. Peculiar trends such as Explainable AI, Automated ML, and Continuous Intelligence present the ability to substantially enhance operational proficiency and decision-making.
Published: 2024

8. Border Masculinities : Literary and Visual Representations

Author: Thakkar, Amit, Baker, Brian, Harris, Christopher, Thakkar, Amit, Baker, Brian, and Harris, Christopher
Abstract: This volume collates and examines recent literary and screened representations of what the editors term ‘border masculinities’. It seeks to understand masculine subjectivities, through fiction and screen, within a complex global arena of relationships and fluid movements across multiple boundaries within that arena. It also concerns paradigmatic borders related to class, gender and ethnicities, as well as other theoretical parameters which cut across porous spatial boundaries. The collection contains a range of theoretically informed responses to varying cultural representations of such masculinities in Europe, the Americas, the Caribbean, Australasia and Asia. Thematic and conceptual connections between them are discussed in the introductory chapter and such links are also made between chapters.
Published: 2024

9. On the Road to Y Wladfa : Mobility and Masculinities in Separado!, Patagonia and American Interior

Author: Thakkar, Amit, Baker, Brian, Harris, Chris, Thakkar, Amit, Baker, Brian, and Harris, Chris
Abstract: This essay will analyse two films which take up the relation between modern Wales and Welsh implication in colonialism, which problematises Wales’s own status as a country settled by the English. These two films revisit the Welsh settler communities of Patagonia, known as Y Wladfa, and the ones which did not historically come into being in North America. These films are projects of the Welsh pop/rock artist Gruff Rhys, whose solo work and that of the Super Furry Animals use both English and Cymraeg. Seperado! and American Interior are both documentary road movies, following Rhys as he travels to Patagonia and the United States respectively, in search of family and historical figures that connect contemporary Wales with earlier historical migrations. The essay will consider the playful, fluid masculine subjectivity of Gruff Rhys – who uses disguises, plastic helmets, and puppets in the films – as a revision of traditional Welsh working masculinities. The essay works through the mobile masculinities presented in these films in relation to encounters between popular and traditional music, and music’s potential to articulate new, hybrid Welsh masculinities which counter narratives of trauma and loss, or nostalgia for an imaginary homeland.
Published: 2024

10. Deciphering the molecular mechanisms underlying anti-pathogenic potential of a polyherbal formulation Enteropan® against multidrug-resistant Pseudomonas aeruginosa

Author: Parmar, Sweety, Gajera, Gemini, Thakkar, Nidhi, Palep, Hanmanthrao S., Kothari, Vijay, Parmar, Sweety, Gajera, Gemini, Thakkar, Nidhi, Palep, Hanmanthrao S., and Kothari, Vijay
Abstract: Objective: Anti-pathogenic potential of a polyherbal formulation Enteropan® was investigated against a multidrug-resistant strain of the bacterium Pseudomonas aeruginosa. Methods: Growth, pigment production, antibiotic susceptibility, etc., were assessed through appropriate in vitro assays. Virulence of the test pathogen was assessed employing the nematode worm Caenorhabditis elegans as a model host. Molecular mechanisms underlining the anti-pathogenic activity of the test formulation were elucidated through whole transcriptome analysis of the extract-exposed bacterial culture. Results: Enteropan-pre-exposed P. aeruginosa displayed reduced (~70%↓) virulence towards the model host C. elegans. Enteropan affected various traits like biofilm formation, protein synthesis and secretion, quorum-modulated pigment production, antibiotic susceptibility, nitrogen metabolism, etc., in this pathogen. P. aeruginosa could not develop complete resistance to the virulence-attenuating activity of Enteropan even after repeated exposure to this polyherbal formulation. Whole transcriptome analysis showed 17% of P. aeruginosa genome to get differentially expressed under influence of Enteropan. Major mechanisms through which Enteropan exerted its anti-virulence activity were found to be generation of nitrosative stress, oxidative stress, envelop stress, quorum modulation, disturbance of protein homeostasis and metal homeostasis. Network analysis of the differently expressed genes resulted in identification of 10 proteins with high network centrality as potential targets from among the downregulated genes. Differential expression of genes coding for five (rpoA, tig, rpsB, rpsL, and rpsJ) of these targets was validated through real-time polymerase chain reaction too, and they can further be pursued as potential targets by various drug discovery programmes.
Published: 2024

11. The Relationship Between Rehabilitation and Frailty in Advanced Heart or Lung Disease.

Author: Dinesh, V, Pierce, R, Hespe, L, Thakkar, S, Wong, M, El Sabbagh, L, Honeysett, L, Brown, P, Delbaere, K, Havryk, A, Malouf, M, Macdonald, PS, Dinesh, V, Pierce, R, Hespe, L, Thakkar, S, Wong, M, El Sabbagh, L, Honeysett, L, Brown, P, Delbaere, K, Havryk, A, Malouf, M, and Macdonald, PS
Abstract: BACKGROUND: Frailty increases morbidity and mortality in patients with advanced heart and lung disease. Emerging evidence shows that postoperative cardiac or pulmonary rehabilitation can improve the frailty status of these patients. The aim of this hypothesis-generating study was to test the relationship between prehabilitation and frailty in patients with advanced heart or lung disease referred for heart and lung transplantation. METHODS: The study was a retrospective audit of consecutive patients with advanced heart or lung disease referred for transplant assessment between January 2021 and December 2022. Frailty scores were recorded using Fried's frailty phenotype (range, 0-5), and rehabilitation status of patients at the time of frailty assessment was recorded. RESULTS: Of 286 patients, 124 patients had advanced heart disease (mean age 53 ± 12 y; 82% men) and 162 patients had advanced lung disease (mean age 55 ± 12 y; 43% men). Sixty-nine (24%) patients were robust (score 0), 156 (55%) were prefrail (score, 1-2), and 61 (21%) were frail (score, 3-5). Eighty-two (29%) patients participated in hospital-based rehabilitation, 72 (25%) in home-based rehabilitation, and 132 (46%) in no rehabilitation. Frailty scores were significantly lower in patients participating in hospital-based or home-based rehabilitation compared with patients not participating in rehabilitation (0.8 ± 1.0 versus 0.8 ± 0.9 versus 2.3±1.2, P < 0.0001). CONCLUSIONS: This study shows that patients participating in cardiac or pulmonary rehabilitation are less frail compared with patients not participating in rehabilitation. These findings suggest that prehabilitation could be beneficial for patients awaiting heart or lung transplantation.
Published: 2024

12. A New Way to Compute the Pseudoscalar Screening Mass at Finite Chemical Potential

Author: Hegde, Prasad, Thakkar, Rishabh, Hegde, Prasad, and Thakkar, Rishabh
Abstract: We present a method to calculate the pion screening mass in 2+1-flavor lattice QCD to $\mathcal{O}(\mu^2_\ell)$, where $\mu_\ell$ is the isoscalar chemical potential. Our approach is based on the expression for the free theory pion screening correlator for massless quarks. We use the Taylor expansion method to calculate the screening correlator to $\mathcal{O}(\mu^4_\ell)$. We then extract the $\mathcal{O}(\mu^2_\ell)$ Taylor coefficient of the screening mass from the Taylor coefficients of the correlator, for two temperatures in the range 2 - 3 GeV. Our calculations were done using the Highly Improved Staggered Quark action, and the strange and light quark masses were set respectively to their physical and nearly physical values, corresponding to meson masses $M_{\bar{s}s}=686$ MeV and $M_\pi=160$ MeV., Comment: Contribution to the proceedings of The 40th International Symposium on Lattice Field Theory (Lattice 2023), July 31st - August 4th, 2023, Fermi National Accelerator Laboratory, USA
Published: 2024

13. WorkArena: How Capable Are Web Agents at Solving Common Knowledge Work Tasks?

Author: Drouin, Alexandre, Gasse, Maxime, Caccia, Massimo, Laradji, Issam H., Del Verme, Manuel, Marty, Tom, Boisvert, Léo, Thakkar, Megh, Cappart, Quentin, Vazquez, David, Chapados, Nicolas, Lacoste, Alexandre, Drouin, Alexandre, Gasse, Maxime, Caccia, Massimo, Laradji, Issam H., Del Verme, Manuel, Marty, Tom, Boisvert, Léo, Thakkar, Megh, Cappart, Quentin, Vazquez, David, Chapados, Nicolas, and Lacoste, Alexandre
Abstract: We study the use of large language model-based agents for interacting with software via web browsers. Unlike prior work, we focus on measuring the agents' ability to perform tasks that span the typical daily work of knowledge workers utilizing enterprise software systems. To this end, we propose WorkArena, a remote-hosted benchmark of 29 tasks based on the widely-used ServiceNow platform. We also introduce BrowserGym, an environment for the design and evaluation of such agents, offering a rich set of actions as well as multimodal observations. Our empirical evaluation reveals that while current agents show promise on WorkArena, there remains a considerable gap towards achieving full task automation. Notably, our analysis uncovers a significant performance disparity between open and closed-source LLMs, highlighting a critical area for future exploration and development in the field., Comment: 27 pages, 10 figures, preprint
Published: 2024

14. Content-Centric Prototyping of Generative AI Applications: Emerging Approaches and Challenges in Collaborative Software Teams

Author: Subramonyam, Hari, Thakkar, Divy, Dieber, Jürgen, Sinha, Anoop, Subramonyam, Hari, Thakkar, Divy, Dieber, Jürgen, and Sinha, Anoop
Abstract: Generative AI models are increasingly powering software applications, offering the capability to produce expressive content across varied contexts. However, unlike previous iterations of human-AI design, the emerging design process for generative capabilities primarily hinges on prompt engineering strategies. Given this fundamental shift in approach, our work aims to understand how collaborative software teams set up and apply design guidelines and values, iteratively prototype prompts, and evaluate prompts to achieve desired outcomes. We conducted design studies with 39 industry professionals, including designers, software engineers, and product managers. Our findings reveal a content-centric prototyping approach in which teams begin with the content they want to generate, then identify specific attributes, constraints, and values, and explore methods to give users the ability to influence and interact with those attributes. Based on associated challenges, such as the lack of model interpretability and overfitting the design to examples, we outline considerations for generative AI prototyping.
Published: 2024

15. A Low-Dissipation and Scalable GEMM Accelerator with Silicon Nitride Photonics

Author: Karempudi, Venkata Sai Praneeth, Vatsavai, Sairam Sri, Thakkar, Ishan, Alo, Oluwaseun Adewunmi, Hastings, Jeffrey Todd, Woods, Justin Scott, Karempudi, Venkata Sai Praneeth, Vatsavai, Sairam Sri, Thakkar, Ishan, Alo, Oluwaseun Adewunmi, Hastings, Jeffrey Todd, and Woods, Justin Scott
Abstract: Over the past few years, several microring resonator (MRR)-based analog photonic architectures have been proposed to accelerate general matrix-matrix multiplications (GEMMs), which are found in abundance in deep learning workloads.These architectures have dramatically grown in popularity because they offer exceptional throughput and energy efficiency compared to their electronic counterparts. However, such architectures, due to their traditional realization based on the silicon-on-insulator (SOI) material platform, face two shortcomings. First, the high-index contrast of the SOI platform incurs high scattering losses, which mandates the provisioning of high optical input power.Second, SOI waveguides are susceptible to two-photon absorption, which can incur substantial optical signal losses at moderate-to-high signal fan-in. These shortcomings have severely detrimental effects on the achievable parallelism, throughput, and energy efficiency of SOI MRR-based GEMM accelerators. To address these shortcomings, we present a novel Silicon Nitride (SiN)-Based Photonic GEMM Accelerator called SiNPhAR. SiNPhAR architecture employs SiN-based active and passive devices to implement analog GEMM functions. Since the SiN material exhibits lower index contrast and no TPA, the optical signal losses in our SiNPhAR architecture are very low. This advantage significantly enhances the achievable processing parallelism, throughput, and energy efficiency of SiNPhAR architecture, compared to SOI-based photonic GEMM accelerators from prior work. We quantify and compare these benefits of SiNPhAR architecture via our cross-layer evaluation for a benchmark workload comprising four modern deep neural network models. From the system-level performance analysis, SiNPhAR demonstrates at least 1.7x better throughput FPS while consuming at least 2.8x better energy efficiency (FPS/W) than prior SOI-based GEMM accelerators., Comment: To Appear at ISQED 2024
Published: 2024

16. Multi-line AI-assisted Code Authoring

Author: Dunay, Omer, Cheng, Daniel, Tait, Adam, Thakkar, Parth, Rigby, Peter C, Chiu, Andy, Ahmad, Imad, Ganesan, Arun, Maddila, Chandra, Murali, Vijayaraghavan, Tayyebi, Ali, Nagappan, Nachiappan, Dunay, Omer, Cheng, Daniel, Tait, Adam, Thakkar, Parth, Rigby, Peter C, Chiu, Andy, Ahmad, Imad, Ganesan, Arun, Maddila, Chandra, Murali, Vijayaraghavan, Tayyebi, Ali, and Nagappan, Nachiappan
Abstract: CodeCompose is an AI-assisted code authoring tool powered by large language models (LLMs) that provides inline suggestions to 10's of thousands of developers at Meta. In this paper, we present how we scaled the product from displaying single-line suggestions to multi-line suggestions. This evolution required us to overcome several unique challenges in improving the usability of these suggestions for developers. First, we discuss how multi-line suggestions can have a 'jarring' effect, as the LLM's suggestions constantly move around the developer's existing code, which would otherwise result in decreased productivity and satisfaction. Second, multi-line suggestions take significantly longer to generate; hence we present several innovative investments we made to reduce the perceived latency for users. These model-hosting optimizations sped up multi-line suggestion latency by 2.5x. Finally, we conduct experiments on 10's of thousands of engineers to understand how multi-line suggestions impact the user experience and contrast this with single-line suggestions. Our experiments reveal that (i) multi-line suggestions account for 42% of total characters accepted (despite only accounting for 16% for displayed suggestions) (ii) multi-line suggestions almost doubled the percentage of keystrokes saved for users from 9% to 17%. Multi-line CodeCompose has been rolled out to all engineers at Meta, and less than 1% of engineers have opted out of multi-line suggestions.
Published: 2024

17. HEANA: A Hybrid Time-Amplitude Analog Optical Accelerator with Flexible Dataflows for Energy-Efficient CNN Inference

Author: Vatsavai, Sairam Sri, Karempudi, Venkata Sai Praneeth, Thakkar, Ishan, Vatsavai, Sairam Sri, Karempudi, Venkata Sai Praneeth, and Thakkar, Ishan
Abstract: Several photonic microring resonators (MRRs) based analog accelerators have been proposed to accelerate the inference of integer-quantized CNNs with remarkably higher throughput and energy efficiency compared to their electronic counterparts. However, the existing analog photonic accelerators suffer from three shortcomings: (i) severe hampering of wavelength parallelism due to various crosstalk effects, (ii) inflexibility of supporting various dataflows other than the weight-stationary dataflow, and (iii) failure in fully leveraging the ability of photodetectors to perform in-situ accumulations. These shortcomings collectively hamper the performance and energy efficiency of prior accelerators. To tackle these shortcomings, we present a novel Hybrid timE Amplitude aNalog optical Accelerator, called HEANA. HEANA employs hybrid time-amplitude analog optical multipliers (TAOMs) that increase the flexibility of HEANA to support multiple dataflows. A spectrally hitless arrangement of TAOMs significantly reduces the crosstalk effects, thereby increasing the wavelength parallelism in HEANA. Moreover, HEANA employs our invented balanced photo-charge accumulators (BPCAs) that enable buffer-less, in-situ, temporal accumulations to eliminate the need to use reduction networks in HEANA, relieving it from related latency and energy overheads. Our evaluation for the inference of four modern CNNs indicates that HEANA provides improvements of atleast 66x and 84x in frames-per-second (FPS) and FPS/W (energy-efficiency), respectively, for equal-area comparisons, on gmean over two MRR-based analog CNN accelerators from prior work., Comment: The paper is under review at ACM TODAES
Published: 2024

18. A Comparative Analysis of Microrings Based Incoherent Photonic GEMM Accelerators

Author: Vatsavai, Sairam Sri, Karempudi, Venkata Sai Praneeth, Alo, Oluwaseun Adewunmi, Thakkar, Ishan, Vatsavai, Sairam Sri, Karempudi, Venkata Sai Praneeth, Alo, Oluwaseun Adewunmi, and Thakkar, Ishan
Abstract: Several microring resonator (MRR) based analog photonic architectures have been proposed to accelerate general matrix-matrix multiplications (GEMMs) in deep neural networks with exceptional throughput and energy efficiency. To implement GEMM functions, these MRR-based architectures, in general, manipulate optical signals in five different ways: (i) Splitting (copying) of multiple optical signals to achieve a certain fan-out, (ii) Aggregation (multiplexing) of multiple optical signals to achieve a certain fan-in, (iii) Modulation of optical signals to imprint input values onto analog signal amplitude, (iv) Weighting of modulated optical signals to achieve analog input-weight multiplication, (v) Summation of optical signals. The MRR-based GEMM accelerators undertake the first four ways of signal manipulation in an arbitrary order ignoring the possible impact of the order of these manipulations on their performance. In this paper, we conduct a detailed analysis of accelerator organizations with three different orders of these manipulations: (1) Modulation-Aggregation-Splitting-Weighting (MASW), (2) Aggregation-Splitting-Modulation-Weighting (ASMW), and (3) Splitting-Modulation-Weighting-Aggregation (SMWA). We show that these organizations affect the crosstalk noise and optical signal losses in different magnitudes, which renders these organizations with different levels of processing parallelism at the circuit level, and different magnitudes of throughput and energy-area efficiency at the system level. Our evaluation results for four CNN models show that SMWA organization achieves up to 4.4$\times$, 5$\times$, and 5.2$\times$ better throughput, energy efficiency, and area-energy efficiency, respectively, compared to ASMW and MASW organizations on average., Comment: To Appear at ISQED 2024
Published: 2024

19. Differentially Private and Adversarially Robust Machine Learning: An Empirical Evaluation

Author: Thakkar, Janvi, Zizzo, Giulio, Maffeis, Sergio, Thakkar, Janvi, Zizzo, Giulio, and Maffeis, Sergio
Abstract: Malicious adversaries can attack machine learning models to infer sensitive information or damage the system by launching a series of evasion attacks. Although various work addresses privacy and security concerns, they focus on individual defenses, but in practice, models may undergo simultaneous attacks. This study explores the combination of adversarial training and differentially private training to defend against simultaneous attacks. While differentially-private adversarial training, as presented in DP-Adv, outperforms the other state-of-the-art methods in performance, it lacks formal privacy guarantees and empirical validation. Thus, in this work, we benchmark the performance of this technique using a membership inference attack and empirically show that the resulting approach is as private as non-robust private models. This work also highlights the need to explore privacy guarantees in dynamic training paradigms., Comment: Accepted at PPAI-24: The 5th AAAI Workshop on Privacy-Preserving Artificial Intelligence
Published: 2024

20. Users' Perceptions of Online Child Abuse Detection Mechanisms

Author: Deldari, Elmira, Thakkar, Parth, Yao, Yaxing, Deldari, Elmira, Thakkar, Parth, and Yao, Yaxing
Abstract: Child sexual exploitation and abuse (CSEA) online has become a major safety issue for children to access the Internet. To combat CSEA, electronics services providers (ESP) have implemented various mechanisms to detect child sexual abuse materials (CSAM). However, these mechanisms, despite their capability to prevent the mass distribution of CSAM online, may raise significant privacy concerns among general users. In this paper, we conducted a semi-structured interview study with 23 participants to understand their privacy perceptions of two types of online CSAM detection mechanisms. Our results suggested that users were concerned about the transparency of the detection process, inappropriate access to users' data, and unclear boundaries of such mechanisms. Our results also highlight that, even though the majority of participants choose to sacrifice their privacy for societal benefits, they still have privacy concerns that need to be addressed. We discuss the design and policy implications for ESP to improve users' awareness of the data practices of these mechanisms, alleviate users' privacy concerns, and increase societal benefits.
Published: 2024

21. Efficiently Train ASR Models that Memorize Less and Perform Better with Per-core Clipping

Author: Wang, Lun, Thakkar, Om, Meng, Zhong, Rafidi, Nicole, Prabhavalkar, Rohit, Narayanan, Arun, Wang, Lun, Thakkar, Om, Meng, Zhong, Rafidi, Nicole, Prabhavalkar, Rohit, and Narayanan, Arun
Abstract: Gradient clipping plays a vital role in training large-scale automatic speech recognition (ASR) models. It is typically applied to minibatch gradients to prevent gradient explosion, and to the individual sample gradients to mitigate unintended memorization. This work systematically investigates the impact of a specific granularity of gradient clipping, namely per-core clip-ping (PCC), across training a wide range of ASR models. We empirically demonstrate that PCC can effectively mitigate unintended memorization in ASR models. Surprisingly, we find that PCC positively influences ASR performance metrics, leading to improved convergence rates and reduced word error rates. To avoid tuning the additional hyperparameter introduced by PCC, we further propose a novel variant, adaptive per-core clipping (APCC), for streamlined optimization. Our findings highlight the multifaceted benefits of PCC as a strategy for robust, privacy-forward ASR model training., Comment: Accepted to Interspeech'24
Published: 2024

22. M2SA: Multimodal and Multilingual Model for Sentiment Analysis of Tweets

Author: Thakkar, Gaurish, Hakimov, Sherzod, Tadić, Marko, Thakkar, Gaurish, Hakimov, Sherzod, and Tadić, Marko
Abstract: In recent years, multimodal natural language processing, aimed at learning from diverse data types, has garnered significant attention. However, there needs to be more clarity when it comes to analysing multimodal tasks in multi-lingual contexts. While prior studies on sentiment analysis of tweets have predominantly focused on the English language, this paper addresses this gap by transforming an existing textual Twitter sentiment dataset into a multimodal format through a straightforward curation process. Our work opens up new avenues for sentiment-related research within the research community. Additionally, we conduct baseline experiments utilising this augmented dataset and report the findings. Notably, our evaluations reveal that when comparing unimodal and multimodal configurations, using a sentiment-tuned large language model as a text encoder performs exceptionally well.
Published: 2024

23. Noise Masking Attacks and Defenses for Pretrained Speech Models

Author: Jagielski, Matthew, Thakkar, Om, Wang, Lun, Jagielski, Matthew, Thakkar, Om, and Wang, Lun
Abstract: Speech models are often trained on sensitive data in order to improve model performance, leading to potential privacy leakage. Our work considers noise masking attacks, introduced by Amid et al. 2022, which attack automatic speech recognition (ASR) models by requesting a transcript of an utterance which is partially replaced with noise. They show that when a record has been seen at training time, the model will transcribe the noisy record with its memorized sensitive transcript. In our work, we extend these attacks beyond ASR models, to attack pretrained speech encoders. Our method fine-tunes the encoder to produce an ASR model, and then performs noise masking on this model, which we find recovers private information from the pretraining data, despite the model never having seen transcripts at pretraining time! We show how to improve the precision of these attacks and investigate a number of countermeasures to our attacks., Comment: accepted to ICASSP 2024
Published: 2024

24. Assessment and Prediction of Cardiovascular Contributions to Severe Maternal Morbidity.

Author: Thakkar, Aarti, Thakkar, Aarti, Hameed, Afshan, Makshood, Minhal, Gudenkauf, Brent, Creanga, Andreea, Malhamé, Isabelle, Grandi, Sonia, Thorne, Sara, DSouza, Rohan, Sharma, Garima, Thakkar, Aarti, Thakkar, Aarti, Hameed, Afshan, Makshood, Minhal, Gudenkauf, Brent, Creanga, Andreea, Malhamé, Isabelle, Grandi, Sonia, Thorne, Sara, DSouza, Rohan, and Sharma, Garima
Abstract: Severe maternal morbidity (SMM) refers to any unexpected outcome directly related to pregnancy and childbirth that results in both short-term delivery complications and long-term consequences to a womens health. This affects about 60,000 women annually in the United States. Cardiovascular contributions to SMM including cardiac arrest, arrhythmia, and acute myocardial infarction are on the rise, probably driven by changing demographics of the pregnant population including more women of extreme maternal age and an increased prevalence of cardiometabolic and structural heart disease. The utilization of SMM prediction tools and risk scores specific to cardiovascular disease in pregnancy has helped with risk stratification. Furthermore, health system data monitoring and reporting to identify and assess etiologies of cardiovascular complications has led to improvement in outcomes and greater standardization of care for mothers with cardiovascular disease. Improving cardiovascular disease-related SMM relies on a multipronged approach comprised of patient-level identification of risk factors, individualized review of SMM cases, and validation of risk stratification tools and system-wide improvements in quality of care. In this article, we review the epidemiology and cardiac causes of SMM, we provide a framework of risk prediction clinical tools, and we highlight need for organization of care to improve outcomes.
Published: 2023

25. Body composition and lung cancer-associated cachexia in TRACERx

Author: Al-Sawaf, O, Weiss, J, Skrzypski, M, Lam, J, Karasaki, T, Zambrana, F, Kidd, A, Frankell, A, Watkins, T, Martinez-Ruiz, C, Puttick, C, Black, J, Huebner, A, Bakir, M, Sokac, M, Collins, S, Veeriah, S, Magno, N, Naceur-Lombardelli, C, Prymas, P, Toncheva, A, Ward, S, Jayanth, N, Salgado, R, Bridge, C, Christiani, D, Mak, R, Bay, C, Rosenthal, M, Sattar, N, Welsh, P, Liu, Y, Perrimon, N, Popuri, K, Beg, M, Mcgranahan, N, Hackshaw, A, Breen, D, O'Rahilly, S, Birkbak, N, Aerts, H, Lester, J, Bajaj, A, Nakas, A, Sodha-Ramdeen, A, Ang, K, Tufail, M, Chowdhry, M, Scotland, M, Boyles, R, Rathinam, S, Wilson, C, Marrone, D, Dulloo, S, Fennell, D, Matharu, G, Shaw, J, Riley, J, Primrose, L, Boleti, E, Cheyne, H, Khalil, M, Richardson, S, Cruickshank, T, Price, G, Kerr, K, Benafif, S, Gilbert, K, Naidu, B, Patel, A, Osman, A, Lacson, C, Langman, G, Shackleford, H, Djearaman, M, Kadiri, S, Middleton, G, Leek, A, Hodgkinson, J, Totten, N, Montero, A, Smith, E, Fontaine, E, Granato, F, Doran, H, Novasio, J, Rammohan, K, Joseph, L, Bishop, P, Shah, R, Moss, S, Joshi, V, Crosbie, P, Gomes, F, Brown, K, Carter, M, Chaturvedi, A, Priest, L, Oliveira, P, Lindsay, C, Blackhall, F, Krebs, M, Summers, Y, Clipson, A, Tugwood, J, Kerr, A, Rothwell, D, Kilgour, E, Dive, C, Schwarz, R, Kaufmann, T, Wilson, G, Rosenthal, R, Van Loo, P, Szallasi, Z, Kisistok, J, Diossy, M, Demeulemeester, J, Bunkum, A, Stewart, A, Magness, A, Rowan, A, Karamani, A, Chain, B, Campbell, B, Castignani, C, Bailey, C, Abbosh, C, Weeden, C, Lee, C, Richard, C, Hiley, C, Moore, D, Pearce, D, Karagianni, D, Biswas, D, Levi, D, Hoxha, E, Cadieux, E, Lim, E, Colliver, E, Nye, E, Gronroos, E, Galvez-Cancino, F, Athanasopoulou, F, Gimeno-Valiente, F, Kassiotis, G, Stavrou, G, Mastrokalos, G, Zhai, H, Lowe, H, Matos, I, Goldman, J, Reading, J, Herrero, J, Rane, J, Nicod, J, Hartley, J, Peggs, K, Enfield, K, Selvaraju, K, Thol, K, Litchfield, K, Ng, K, Chen, K, Dijkstra, K, Grigoriadis, K, Thakkar, K, Ensell, L, Shah, M, Duran, M, Litovchenko, M, Sunderland, M, Hill, M, Dietzen, M, Leung, M, Escudero, M, Angelova, M, Tanic, M, Sivakumar, M, Kanu, N, Chervova, O, Lucas, O, Pich, O, Hobson, P, Pawlik, P, Stone, R, Bentham, R, Hynds, R, Vendramin, R, Saghafinia, S, Lopez, S, Gamble, S, Ung, S, Quezada, S, Vanloo, S, Zaccaria, S, Hessey, S, Boeing, S, Beck, S, Bola, S, Denner, T, Marafioti, T, Mourikis, T, Spanswick, V, Barbe, V, Lu, W, Hill, W, Liu, W, Wu, Y, Naito, Y, Ramsden, Z, Veiga, C, Royle, G, Collins-Fekete, C, Fraioli, F, Ashford, P, Clark, T, Forster, M, Lee, S, Borg, E, Falzon, M, Papadatos-Pastos, D, Wilson, J, Ahmad, T, Procter, A, Ahmed, A, Taylor, M, Nair, A, Lawrence, D, Patrini, D, Navani, N, Thakrar, R, Janes, S, Hoogenboom, E, Monk, F, Holding, J, Choudhary, J, Bhakhri, K, Scarci, M, Hayward, M, Panagiotopoulos, N, Gorman, P, Khiroya, R, Stephens, R, Wong, Y, Bandula, S, Sharp, A, Smith, S, Gower, N, Dhanda, H, Chan, K, Pilotti, C, Leslie, R, Grapa, A, Zhang, H, Abduljabbar, K, Pan, X, Yuan, Y, Chuter, D, Mackenzie, M, Chee, S, Alzetani, A, Cave, J, Scarlett, L, Richards, J, Ingram, P, Austin, S, De Sousa, P, Jordan, S, Rice, A, Raubenheimer, H, Bhayani, H, Ambrose, L, Devaraj, A, Chavan, H, Begum, S, Buderi, S, Kaniu, D, Malima, M, Booth, S, Nicholson, A, Fernandes, N, Shah, P, Proli, C, Hewish, M, Danson, S, Shackcloth, M, Robinson, L, Russell, P, Blyth, K, Dick, C, Le Quesne, J, Kirk, A, Asif, M, Bilancia, R, Kostoulas, N, Thomas, M, Jamal-Hanjani, M, Swanton, C, Al-Sawaf O., Weiss J., Skrzypski M., Lam J. M., Karasaki T., Zambrana F., Kidd A. C., Frankell A. M., Watkins T. B. K., Martinez-Ruiz C., Puttick C., Black J. R. M., Huebner A., Bakir M. A., Sokac M., Collins S., Veeriah S., Magno N., Naceur-Lombardelli C., Prymas P., Toncheva A., Ward S., Jayanth N., Salgado R., Bridge C. P., Christiani D. C., Mak R. H., Bay C., Rosenthal M., Sattar N., Welsh P., Liu Y., Perrimon N., Popuri K., Beg M. F., McGranahan N., Hackshaw A., Breen D. M., O'Rahilly S., Birkbak N. J., Aerts H. J. W. L., Aerts H. J., Lester J. F., Bajaj A., Nakas A., Sodha-Ramdeen A., Ang K., Tufail M., Chowdhry M. F., Scotland M., Boyles R., Rathinam S., Wilson C., Marrone D., Dulloo S., Fennell D. A., Matharu G., Shaw J. A., Riley J., Primrose L., Boleti E., Cheyne H., Khalil M., Richardson S., Cruickshank T., Price G., Kerr K. M., Benafif S., Gilbert K., Naidu B., Patel A. J., Osman A., Lacson C., Langman G., Shackleford H., Djearaman M., Kadiri S., Middleton G., Leek A., Hodgkinson J. D., Totten N., Montero A., Smith E., Fontaine E., Granato F., Doran H., Novasio J., Rammohan K., Joseph L., Bishop P., Shah R., Moss S., Joshi V., Crosbie P., Gomes F., Brown K., Carter M., Chaturvedi A., Priest L., Oliveira P., Lindsay C. R., Blackhall F. H., Krebs M. G., Summers Y., Clipson A., Tugwood J., Kerr A., Rothwell D. G., Kilgour E., Dive C., Schwarz R. F., Kaufmann T. L., Wilson G. A., Rosenthal R., Van Loo P., Szallasi Z., Kisistok J., Diossy M., Demeulemeester J., Bunkum A., Stewart A., Magness A., Rowan A., Karamani A., Chain B., Campbell B. B., Castignani C., Bailey C., Abbosh C., Weeden C. E., Lee C., Richard C., Hiley C. T., Moore D. A., Pearce D. R., Karagianni D., Biswas D., Levi D., Hoxha E., Cadieux E. L., Lim E. L., Colliver E., Nye E., Gronroos E., Galvez-Cancino F., Athanasopoulou F., Gimeno-Valiente F., Kassiotis G., Stavrou G., Mastrokalos G., Zhai H., Lowe H. L., Matos I. G., Goldman J., Reading J. L., Herrero J., Rane J. K., Nicod J., Hartley J. A., Peggs K. S., Enfield K. S. S., Selvaraju K., Thol K., Litchfield K., Ng K. W., Chen K., Dijkstra K., Grigoriadis K., Thakkar K., Ensell L., Shah M., Duran M. V., Litovchenko M., Sunderland M. W., Hill M. S., Dietzen M., Leung M., Escudero M., Angelova M., Tanic M., Sivakumar M., Kanu N., Chervova O., Lucas O., Pich O., Hobson P., Pawlik P., Stone R. K., Bentham R., Hynds R. E., Vendramin R., Saghafinia S., Lopez S., Gamble S., Ung S. K. A., Quezada S. A., Vanloo S., Zaccaria S., Hessey S., Boeing S., Beck S., Bola S. K., Denner T., Marafioti T., Mourikis T. P., Spanswick V., Barbe V., Lu W. -T., Hill W., Liu W. K., Wu Y., Naito Y., Ramsden Z., Veiga C., Royle G., Collins-Fekete C. -A., Fraioli F., Ashford P., Clark T., Forster M. D., Lee S. M., Borg E., Falzon M., Papadatos-Pastos D., Wilson J., Ahmad T., Procter A. J., Ahmed A., Taylor M. N., Nair A., Lawrence D., Patrini D., Navani N., Thakrar R. M., Janes S. M., Hoogenboom E. M., Monk F., Holding J. W., Choudhary J., Bhakhri K., Scarci M., Hayward M., Panagiotopoulos N., Gorman P., Khiroya R., Stephens R. C., Wong Y. N. S., Bandula S., Sharp A., Smith S., Gower N., Dhanda H. K., Chan K., Pilotti C., Leslie R., Grapa A., Zhang H., AbdulJabbar K., Pan X., Yuan Y., Chuter D., MacKenzie M., Chee S., Alzetani A., Cave J., Scarlett L., Richards J., Ingram P., Austin S., Lim E., De Sousa P., Jordan S., Rice A., Raubenheimer H., Bhayani H., Ambrose L., Devaraj A., Chavan H., Begum S., Buderi S. I., Kaniu D., Malima M., Booth S., Nicholson A. G., Fernandes N., Shah P., Proli C., Hewish M., Danson S., Shackcloth M. J., Robinson L., Russell P., Blyth K. G., Dick C., Le Quesne J., Kirk A., Asif M., Bilancia R., Kostoulas N., Thomas M., Jamal-Hanjani M., Swanton C., Al-Sawaf, O, Weiss, J, Skrzypski, M, Lam, J, Karasaki, T, Zambrana, F, Kidd, A, Frankell, A, Watkins, T, Martinez-Ruiz, C, Puttick, C, Black, J, Huebner, A, Bakir, M, Sokac, M, Collins, S, Veeriah, S, Magno, N, Naceur-Lombardelli, C, Prymas, P, Toncheva, A, Ward, S, Jayanth, N, Salgado, R, Bridge, C, Christiani, D, Mak, R, Bay, C, Rosenthal, M, Sattar, N, Welsh, P, Liu, Y, Perrimon, N, Popuri, K, Beg, M, Mcgranahan, N, Hackshaw, A, Breen, D, O'Rahilly, S, Birkbak, N, Aerts, H, Lester, J, Bajaj, A, Nakas, A, Sodha-Ramdeen, A, Ang, K, Tufail, M, Chowdhry, M, Scotland, M, Boyles, R, Rathinam, S, Wilson, C, Marrone, D, Dulloo, S, Fennell, D, Matharu, G, Shaw, J, Riley, J, Primrose, L, Boleti, E, Cheyne, H, Khalil, M, Richardson, S, Cruickshank, T, Price, G, Kerr, K, Benafif, S, Gilbert, K, Naidu, B, Patel, A, Osman, A, Lacson, C, Langman, G, Shackleford, H, Djearaman, M, Kadiri, S, Middleton, G, Leek, A, Hodgkinson, J, Totten, N, Montero, A, Smith, E, Fontaine, E, Granato, F, Doran, H, Novasio, J, Rammohan, K, Joseph, L, Bishop, P, Shah, R, Moss, S, Joshi, V, Crosbie, P, Gomes, F, Brown, K, Carter, M, Chaturvedi, A, Priest, L, Oliveira, P, Lindsay, C, Blackhall, F, Krebs, M, Summers, Y, Clipson, A, Tugwood, J, Kerr, A, Rothwell, D, Kilgour, E, Dive, C, Schwarz, R, Kaufmann, T, Wilson, G, Rosenthal, R, Van Loo, P, Szallasi, Z, Kisistok, J, Diossy, M, Demeulemeester, J, Bunkum, A, Stewart, A, Magness, A, Rowan, A, Karamani, A, Chain, B, Campbell, B, Castignani, C, Bailey, C, Abbosh, C, Weeden, C, Lee, C, Richard, C, Hiley, C, Moore, D, Pearce, D, Karagianni, D, Biswas, D, Levi, D, Hoxha, E, Cadieux, E, Lim, E, Colliver, E, Nye, E, Gronroos, E, Galvez-Cancino, F, Athanasopoulou, F, Gimeno-Valiente, F, Kassiotis, G, Stavrou, G, Mastrokalos, G, Zhai, H, Lowe, H, Matos, I, Goldman, J, Reading, J, Herrero, J, Rane, J, Nicod, J, Hartley, J, Peggs, K, Enfield, K, Selvaraju, K, Thol, K, Litchfield, K, Ng, K, Chen, K, Dijkstra, K, Grigoriadis, K, Thakkar, K, Ensell, L, Shah, M, Duran, M, Litovchenko, M, Sunderland, M, Hill, M, Dietzen, M, Leung, M, Escudero, M, Angelova, M, Tanic, M, Sivakumar, M, Kanu, N, Chervova, O, Lucas, O, Pich, O, Hobson, P, Pawlik, P, Stone, R, Bentham, R, Hynds, R, Vendramin, R, Saghafinia, S, Lopez, S, Gamble, S, Ung, S, Quezada, S, Vanloo, S, Zaccaria, S, Hessey, S, Boeing, S, Beck, S, Bola, S, Denner, T, Marafioti, T, Mourikis, T, Spanswick, V, Barbe, V, Lu, W, Hill, W, Liu, W, Wu, Y, Naito, Y, Ramsden, Z, Veiga, C, Royle, G, Collins-Fekete, C, Fraioli, F, Ashford, P, Clark, T, Forster, M, Lee, S, Borg, E, Falzon, M, Papadatos-Pastos, D, Wilson, J, Ahmad, T, Procter, A, Ahmed, A, Taylor, M, Nair, A, Lawrence, D, Patrini, D, Navani, N, Thakrar, R, Janes, S, Hoogenboom, E, Monk, F, Holding, J, Choudhary, J, Bhakhri, K, Scarci, M, Hayward, M, Panagiotopoulos, N, Gorman, P, Khiroya, R, Stephens, R, Wong, Y, Bandula, S, Sharp, A, Smith, S, Gower, N, Dhanda, H, Chan, K, Pilotti, C, Leslie, R, Grapa, A, Zhang, H, Abduljabbar, K, Pan, X, Yuan, Y, Chuter, D, Mackenzie, M, Chee, S, Alzetani, A, Cave, J, Scarlett, L, Richards, J, Ingram, P, Austin, S, De Sousa, P, Jordan, S, Rice, A, Raubenheimer, H, Bhayani, H, Ambrose, L, Devaraj, A, Chavan, H, Begum, S, Buderi, S, Kaniu, D, Malima, M, Booth, S, Nicholson, A, Fernandes, N, Shah, P, Proli, C, Hewish, M, Danson, S, Shackcloth, M, Robinson, L, Russell, P, Blyth, K, Dick, C, Le Quesne, J, Kirk, A, Asif, M, Bilancia, R, Kostoulas, N, Thomas, M, Jamal-Hanjani, M, Swanton, C, Al-Sawaf O., Weiss J., Skrzypski M., Lam J. M., Karasaki T., Zambrana F., Kidd A. C., Frankell A. M., Watkins T. B. K., Martinez-Ruiz C., Puttick C., Black J. R. M., Huebner A., Bakir M. A., Sokac M., Collins S., Veeriah S., Magno N., Naceur-Lombardelli C., Prymas P., Toncheva A., Ward S., Jayanth N., Salgado R., Bridge C. P., Christiani D. C., Mak R. H., Bay C., Rosenthal M., Sattar N., Welsh P., Liu Y., Perrimon N., Popuri K., Beg M. F., McGranahan N., Hackshaw A., Breen D. M., O'Rahilly S., Birkbak N. J., Aerts H. J. W. L., Aerts H. J., Lester J. F., Bajaj A., Nakas A., Sodha-Ramdeen A., Ang K., Tufail M., Chowdhry M. F., Scotland M., Boyles R., Rathinam S., Wilson C., Marrone D., Dulloo S., Fennell D. A., Matharu G., Shaw J. A., Riley J., Primrose L., Boleti E., Cheyne H., Khalil M., Richardson S., Cruickshank T., Price G., Kerr K. M., Benafif S., Gilbert K., Naidu B., Patel A. J., Osman A., Lacson C., Langman G., Shackleford H., Djearaman M., Kadiri S., Middleton G., Leek A., Hodgkinson J. D., Totten N., Montero A., Smith E., Fontaine E., Granato F., Doran H., Novasio J., Rammohan K., Joseph L., Bishop P., Shah R., Moss S., Joshi V., Crosbie P., Gomes F., Brown K., Carter M., Chaturvedi A., Priest L., Oliveira P., Lindsay C. R., Blackhall F. H., Krebs M. G., Summers Y., Clipson A., Tugwood J., Kerr A., Rothwell D. G., Kilgour E., Dive C., Schwarz R. F., Kaufmann T. L., Wilson G. A., Rosenthal R., Van Loo P., Szallasi Z., Kisistok J., Diossy M., Demeulemeester J., Bunkum A., Stewart A., Magness A., Rowan A., Karamani A., Chain B., Campbell B. B., Castignani C., Bailey C., Abbosh C., Weeden C. E., Lee C., Richard C., Hiley C. T., Moore D. A., Pearce D. R., Karagianni D., Biswas D., Levi D., Hoxha E., Cadieux E. L., Lim E. L., Colliver E., Nye E., Gronroos E., Galvez-Cancino F., Athanasopoulou F., Gimeno-Valiente F., Kassiotis G., Stavrou G., Mastrokalos G., Zhai H., Lowe H. L., Matos I. G., Goldman J., Reading J. L., Herrero J., Rane J. K., Nicod J., Hartley J. A., Peggs K. S., Enfield K. S. S., Selvaraju K., Thol K., Litchfield K., Ng K. W., Chen K., Dijkstra K., Grigoriadis K., Thakkar K., Ensell L., Shah M., Duran M. V., Litovchenko M., Sunderland M. W., Hill M. S., Dietzen M., Leung M., Escudero M., Angelova M., Tanic M., Sivakumar M., Kanu N., Chervova O., Lucas O., Pich O., Hobson P., Pawlik P., Stone R. K., Bentham R., Hynds R. E., Vendramin R., Saghafinia S., Lopez S., Gamble S., Ung S. K. A., Quezada S. A., Vanloo S., Zaccaria S., Hessey S., Boeing S., Beck S., Bola S. K., Denner T., Marafioti T., Mourikis T. P., Spanswick V., Barbe V., Lu W. -T., Hill W., Liu W. K., Wu Y., Naito Y., Ramsden Z., Veiga C., Royle G., Collins-Fekete C. -A., Fraioli F., Ashford P., Clark T., Forster M. D., Lee S. M., Borg E., Falzon M., Papadatos-Pastos D., Wilson J., Ahmad T., Procter A. J., Ahmed A., Taylor M. N., Nair A., Lawrence D., Patrini D., Navani N., Thakrar R. M., Janes S. M., Hoogenboom E. M., Monk F., Holding J. W., Choudhary J., Bhakhri K., Scarci M., Hayward M., Panagiotopoulos N., Gorman P., Khiroya R., Stephens R. C., Wong Y. N. S., Bandula S., Sharp A., Smith S., Gower N., Dhanda H. K., Chan K., Pilotti C., Leslie R., Grapa A., Zhang H., AbdulJabbar K., Pan X., Yuan Y., Chuter D., MacKenzie M., Chee S., Alzetani A., Cave J., Scarlett L., Richards J., Ingram P., Austin S., Lim E., De Sousa P., Jordan S., Rice A., Raubenheimer H., Bhayani H., Ambrose L., Devaraj A., Chavan H., Begum S., Buderi S. I., Kaniu D., Malima M., Booth S., Nicholson A. G., Fernandes N., Shah P., Proli C., Hewish M., Danson S., Shackcloth M. J., Robinson L., Russell P., Blyth K. G., Dick C., Le Quesne J., Kirk A., Asif M., Bilancia R., Kostoulas N., Thomas M., Jamal-Hanjani M., and Swanton C.
Abstract: Cancer-associated cachexia (CAC) is a major contributor to morbidity and mortality in individuals with non-small cell lung cancer. Key features of CAC include alterations in body composition and body weight. Here, we explore the association between body composition and body weight with survival and delineate potential biological processes and mediators that contribute to the development of CAC. Computed tomography-based body composition analysis of 651 individuals in the TRACERx (TRAcking non-small cell lung Cancer Evolution through therapy (Rx)) study suggested that individuals in the bottom 20th percentile of the distribution of skeletal muscle or adipose tissue area at the time of lung cancer diagnosis, had significantly shorter lung cancer-specific survival and overall survival. This finding was validated in 420 individuals in the independent Boston Lung Cancer Study. Individuals classified as having developed CAC according to one or more features at relapse encompassing loss of adipose or muscle tissue, or body mass index-adjusted weight loss were found to have distinct tumor genomic and transcriptomic profiles compared with individuals who did not develop such features. Primary non-small cell lung cancers from individuals who developed CAC were characterized by enrichment of inflammatory signaling and epithelial–mesenchymal transitional pathways, and differentially expressed genes upregulated in these tumors included cancer-testis antigen MAGEA6 and matrix metalloproteinases, such as ADAMTS3. In an exploratory proteomic analysis of circulating putative mediators of cachexia performed in a subset of 110 individuals from TRACERx, a significant association between circulating GDF15 and loss of body weight, skeletal muscle and adipose tissue was identified at relapse, supporting the potential therapeutic relevance of targeting GDF15 in the management of CAC.
Published: 2023

26. Evolutionary characterization of lung adenocarcinoma morphology in TRACERx

Author: Karasaki, T, Moore, D, Veeriah, S, Naceur-Lombardelli, C, Toncheva, A, Magno, N, Ward, S, Bakir, M, Watkins, T, Grigoriadis, K, Huebner, A, Hill, M, Frankell, A, Abbosh, C, Puttick, C, Zhai, H, Gimeno-Valiente, F, Saghafinia, S, Kanu, N, Dietzen, M, Pich, O, Lim, E, Martinez-Ruiz, C, Black, J, Biswas, D, Campbell, B, Lee, C, Colliver, E, Enfield, K, Hessey, S, Hiley, C, Zaccaria, S, Litchfield, K, Birkbak, N, Cadieux, E, Demeulemeester, J, Van Loo, P, Adusumilli, P, Tan, K, Cheema, W, Sanchez-Vega, F, Jones, D, Rekhtman, N, Travis, W, Hackshaw, A, Marafioti, T, Salgado, R, Le Quesne, J, Nicholson, A, Lester, J, Bajaj, A, Nakas, A, Sodha-Ramdeen, A, Ang, K, Tufail, M, Chowdhry, M, Scotland, M, Boyles, R, Rathinam, S, Wilson, C, Marrone, D, Dulloo, S, Fennell, D, Matharu, G, Shaw, J, Riley, J, Primrose, L, Boleti, E, Cheyne, H, Khalil, M, Richardson, S, Cruickshank, T, Price, G, Kerr, K, Benafif, S, Gilbert, K, Naidu, B, Patel, A, Osman, A, Lacson, C, Langman, G, Shackleford, H, Djearaman, M, Kadiri, S, Middleton, G, Leek, A, Hodgkinson, J, Totten, N, Montero, A, Smith, E, Fontaine, E, Granato, F, Doran, H, Novasio, J, Rammohan, K, Joseph, L, Bishop, P, Shah, R, Moss, S, Joshi, V, Crosbie, P, Gomes, F, Brown, K, Carter, M, Chaturvedi, A, Priest, L, Oliveira, P, Lindsay, C, Blackhall, F, Krebs, M, Summers, Y, Clipson, A, Tugwood, J, Kerr, A, Rothwell, D, Kilgour, E, Dive, C, Aerts, H, Schwarz, R, Kaufmann, T, Wilson, G, Rosenthal, R, Szallasi, Z, Kisistok, J, Sokac, M, Diossy, M, Bunkum, A, Stewart, A, Magness, A, Rowan, A, Karamani, A, Chain, B, Castignani, C, Bailey, C, Weeden, C, Richard, C, Pearce, D, Karagianni, D, Levi, D, Hoxha, E, Nye, E, Gronroos, E, Galvez-Cancino, F, Athanasopoulou, F, Kassiotis, G, Stavrou, G, Mastrokalos, G, Lowe, H, Matos, I, Goldman, J, Reading, J, Herrero, J, Rane, J, Nicod, J, Lam, J, Hartley, J, Peggs, K, Selvaraju, K, Thol, K, Ng, K, Chen, K, Dijkstra, K, Thakkar, K, Ensell, L, Shah, M, Duran, M, Litovchenko, M, Sunderland, M, Leung, M, Escudero, M, Angelova, M, Tanic, M, Sivakumar, M, Chervova, O, Lucas, O, Al-Sawaf, O, Prymas, P, Hobson, P, Pawlik, P, Stone, R, Bentham, R, Hynds, R, Vendramin, R, Lopez, S, Gamble, S, Ung, S, Quezada, S, Vanloo, S, Boeing, S, Beck, S, Bola, S, Denner, T, Mourikis, T, Spanswick, V, Barbe, V, Lu, W, Hill, W, Liu, W, Wu, Y, Naito, Y, Ramsden, Z, Veiga, C, Royle, G, Collins-Fekete, C, Fraioli, F, Ashford, P, Clark, T, Forster, M, Lee, S, Borg, E, Falzon, M, Papadatos-Pastos, D, Wilson, J, Ahmad, T, Procter, A, Ahmed, A, Taylor, M, Nair, A, Lawrence, D, Patrini, D, Navani, N, Thakrar, R, Janes, S, Hoogenboom, E, Monk, F, Holding, J, Choudhary, J, Bhakhri, K, Scarci, M, Hayward, M, Panagiotopoulos, N, Gorman, P, Khiroya, R, Stephens, R, Wong, Y, Bandula, S, Sharp, A, Smith, S, Gower, N, Dhanda, H, Chan, K, Pilotti, C, Leslie, R, Grapa, A, Zhang, H, Abduljabbar, K, Pan, X, Yuan, Y, Chuter, D, Mackenzie, M, Chee, S, Alzetani, A, Cave, J, Scarlett, L, Richards, J, Ingram, P, Austin, S, De Sousa, P, Jordan, S, Rice, A, Raubenheimer, H, Bhayani, H, Ambrose, L, Devaraj, A, Chavan, H, Begum, S, Buderi, S, Kaniu, D, Malima, M, Booth, S, Fernandes, N, Shah, P, Proli, C, Hewish, M, Danson, S, Shackcloth, M, Robinson, L, Russell, P, Blyth, K, Dick, C, Kirk, A, Asif, M, Bilancia, R, Kostoulas, N, Thomas, M, Mcgranahan, N, Swanton, C, Jamal-Hanjani, M, Karasaki T., Moore D. A., Veeriah S., Naceur-Lombardelli C., Toncheva A., Magno N., Ward S., Bakir M. A., Watkins T. B. K., Grigoriadis K., Huebner A., Hill M. S., Frankell A. M., Abbosh C., Puttick C., Zhai H., Gimeno-Valiente F., Saghafinia S., Kanu N., Dietzen M., Pich O., Lim E. L., Martinez-Ruiz C., Black J. R. M., Biswas D., Campbell B. B., Lee C., Colliver E., Enfield K. S. S., Hessey S., Hiley C. T., Zaccaria S., Litchfield K., Birkbak N. J., Cadieux E. L., Demeulemeester J., Van Loo P., Adusumilli P. S., Tan K. S., Cheema W., Sanchez-Vega F., Jones D. R., Rekhtman N., Travis W. D., Hackshaw A., Marafioti T., Salgado R., Le Quesne J., Nicholson A. G., Lester J. F., Bajaj A., Nakas A., Sodha-Ramdeen A., Ang K., Tufail M., Chowdhry M. F., Scotland M., Boyles R., Rathinam S., Wilson C., Marrone D., Dulloo S., Fennell D. A., Matharu G., Shaw J. A., Riley J., Primrose L., Boleti E., Cheyne H., Khalil M., Richardson S., Cruickshank T., Price G., Kerr K. M., Benafif S., Gilbert K., Naidu B., Patel A. J., Osman A., Lacson C., Langman G., Shackleford H., Djearaman M., Kadiri S., Middleton G., Leek A., Hodgkinson J. D., Totten N., Montero A., Smith E., Fontaine E., Granato F., Doran H., Novasio J., Rammohan K., Joseph L., Bishop P., Shah R., Moss S., Joshi V., Crosbie P., Gomes F., Brown K., Carter M., Chaturvedi A., Priest L., Oliveira P., Lindsay C. R., Blackhall F. H., Krebs M. G., Summers Y., Clipson A., Tugwood J., Kerr A., Rothwell D. G., Kilgour E., Dive C., Aerts H. J. W. L., Schwarz R. F., Kaufmann T. L., Wilson G. A., Rosenthal R., Szallasi Z., Kisistok J., Sokac M., Diossy M., Bunkum A., Stewart A., Magness A., Rowan A., Karamani A., Chain B., Castignani C., Bailey C., Weeden C. E., Richard C., Pearce D. R., Karagianni D., Levi D., Hoxha E., Nye E., Gronroos E., Galvez-Cancino F., Athanasopoulou F., Kassiotis G., Stavrou G., Mastrokalos G., Lowe H. L., Matos I. G., Goldman J., Reading J. L., Herrero J., Rane J. K., Nicod J., Lam J. M., Hartley J. A., Peggs K. S., Selvaraju K., Thol K., Ng K. W., Chen K., Dijkstra K., Thakkar K., Ensell L., Shah M., Duran M. V., Litovchenko M., Sunderland M. W., Leung M., Escudero M., Angelova M., Tanic M., Sivakumar M., Chervova O., Lucas O., Al-Sawaf O., Prymas P., Hobson P., Pawlik P., Stone R. K., Bentham R., Hynds R. E., Vendramin R., Lopez S., Gamble S., Ung S. K. A., Quezada S. A., Vanloo S., Boeing S., Beck S., Bola S. K., Denner T., Mourikis T. P., Spanswick V., Barbe V., Lu W. -T., Hill W., Liu W. K., Wu Y., Naito Y., Ramsden Z., Veiga C., Royle G., Collins-Fekete C. -A., Fraioli F., Ashford P., Clark T., Forster M. D., Lee S. M., Borg E., Falzon M., Papadatos-Pastos D., Wilson J., Ahmad T., Procter A. J., Ahmed A., Taylor M. N., Nair A., Lawrence D., Patrini D., Navani N., Thakrar R. M., Janes S. M., Hoogenboom E. M., Monk F., Holding J. W., Choudhary J., Bhakhri K., Scarci M., Hayward M., Panagiotopoulos N., Gorman P., Khiroya R., Stephens R. C., Wong Y. N. S., Bandula S., Sharp A., Smith S., Gower N., Dhanda H. K., Chan K., Pilotti C., Leslie R., Grapa A., Zhang H., AbdulJabbar K., Pan X., Yuan Y., Chuter D., MacKenzie M., Chee S., Alzetani A., Cave J., Scarlett L., Richards J., Ingram P., Austin S., Lim E., De Sousa P., Jordan S., Rice A., Raubenheimer H., Bhayani H., Ambrose L., Devaraj A., Chavan H., Begum S., Buderi S. I., Kaniu D., Malima M., Booth S., Fernandes N., Shah P., Proli C., Hewish M., Danson S., Shackcloth M. J., Robinson L., Russell P., Blyth K. G., Dick C., Kirk A., Asif M., Bilancia R., Kostoulas N., Thomas M., McGranahan N., Swanton C., Jamal-Hanjani M., Karasaki, T, Moore, D, Veeriah, S, Naceur-Lombardelli, C, Toncheva, A, Magno, N, Ward, S, Bakir, M, Watkins, T, Grigoriadis, K, Huebner, A, Hill, M, Frankell, A, Abbosh, C, Puttick, C, Zhai, H, Gimeno-Valiente, F, Saghafinia, S, Kanu, N, Dietzen, M, Pich, O, Lim, E, Martinez-Ruiz, C, Black, J, Biswas, D, Campbell, B, Lee, C, Colliver, E, Enfield, K, Hessey, S, Hiley, C, Zaccaria, S, Litchfield, K, Birkbak, N, Cadieux, E, Demeulemeester, J, Van Loo, P, Adusumilli, P, Tan, K, Cheema, W, Sanchez-Vega, F, Jones, D, Rekhtman, N, Travis, W, Hackshaw, A, Marafioti, T, Salgado, R, Le Quesne, J, Nicholson, A, Lester, J, Bajaj, A, Nakas, A, Sodha-Ramdeen, A, Ang, K, Tufail, M, Chowdhry, M, Scotland, M, Boyles, R, Rathinam, S, Wilson, C, Marrone, D, Dulloo, S, Fennell, D, Matharu, G, Shaw, J, Riley, J, Primrose, L, Boleti, E, Cheyne, H, Khalil, M, Richardson, S, Cruickshank, T, Price, G, Kerr, K, Benafif, S, Gilbert, K, Naidu, B, Patel, A, Osman, A, Lacson, C, Langman, G, Shackleford, H, Djearaman, M, Kadiri, S, Middleton, G, Leek, A, Hodgkinson, J, Totten, N, Montero, A, Smith, E, Fontaine, E, Granato, F, Doran, H, Novasio, J, Rammohan, K, Joseph, L, Bishop, P, Shah, R, Moss, S, Joshi, V, Crosbie, P, Gomes, F, Brown, K, Carter, M, Chaturvedi, A, Priest, L, Oliveira, P, Lindsay, C, Blackhall, F, Krebs, M, Summers, Y, Clipson, A, Tugwood, J, Kerr, A, Rothwell, D, Kilgour, E, Dive, C, Aerts, H, Schwarz, R, Kaufmann, T, Wilson, G, Rosenthal, R, Szallasi, Z, Kisistok, J, Sokac, M, Diossy, M, Bunkum, A, Stewart, A, Magness, A, Rowan, A, Karamani, A, Chain, B, Castignani, C, Bailey, C, Weeden, C, Richard, C, Pearce, D, Karagianni, D, Levi, D, Hoxha, E, Nye, E, Gronroos, E, Galvez-Cancino, F, Athanasopoulou, F, Kassiotis, G, Stavrou, G, Mastrokalos, G, Lowe, H, Matos, I, Goldman, J, Reading, J, Herrero, J, Rane, J, Nicod, J, Lam, J, Hartley, J, Peggs, K, Selvaraju, K, Thol, K, Ng, K, Chen, K, Dijkstra, K, Thakkar, K, Ensell, L, Shah, M, Duran, M, Litovchenko, M, Sunderland, M, Leung, M, Escudero, M, Angelova, M, Tanic, M, Sivakumar, M, Chervova, O, Lucas, O, Al-Sawaf, O, Prymas, P, Hobson, P, Pawlik, P, Stone, R, Bentham, R, Hynds, R, Vendramin, R, Lopez, S, Gamble, S, Ung, S, Quezada, S, Vanloo, S, Boeing, S, Beck, S, Bola, S, Denner, T, Mourikis, T, Spanswick, V, Barbe, V, Lu, W, Hill, W, Liu, W, Wu, Y, Naito, Y, Ramsden, Z, Veiga, C, Royle, G, Collins-Fekete, C, Fraioli, F, Ashford, P, Clark, T, Forster, M, Lee, S, Borg, E, Falzon, M, Papadatos-Pastos, D, Wilson, J, Ahmad, T, Procter, A, Ahmed, A, Taylor, M, Nair, A, Lawrence, D, Patrini, D, Navani, N, Thakrar, R, Janes, S, Hoogenboom, E, Monk, F, Holding, J, Choudhary, J, Bhakhri, K, Scarci, M, Hayward, M, Panagiotopoulos, N, Gorman, P, Khiroya, R, Stephens, R, Wong, Y, Bandula, S, Sharp, A, Smith, S, Gower, N, Dhanda, H, Chan, K, Pilotti, C, Leslie, R, Grapa, A, Zhang, H, Abduljabbar, K, Pan, X, Yuan, Y, Chuter, D, Mackenzie, M, Chee, S, Alzetani, A, Cave, J, Scarlett, L, Richards, J, Ingram, P, Austin, S, De Sousa, P, Jordan, S, Rice, A, Raubenheimer, H, Bhayani, H, Ambrose, L, Devaraj, A, Chavan, H, Begum, S, Buderi, S, Kaniu, D, Malima, M, Booth, S, Fernandes, N, Shah, P, Proli, C, Hewish, M, Danson, S, Shackcloth, M, Robinson, L, Russell, P, Blyth, K, Dick, C, Kirk, A, Asif, M, Bilancia, R, Kostoulas, N, Thomas, M, Mcgranahan, N, Swanton, C, Jamal-Hanjani, M, Karasaki T., Moore D. A., Veeriah S., Naceur-Lombardelli C., Toncheva A., Magno N., Ward S., Bakir M. A., Watkins T. B. K., Grigoriadis K., Huebner A., Hill M. S., Frankell A. M., Abbosh C., Puttick C., Zhai H., Gimeno-Valiente F., Saghafinia S., Kanu N., Dietzen M., Pich O., Lim E. L., Martinez-Ruiz C., Black J. R. M., Biswas D., Campbell B. B., Lee C., Colliver E., Enfield K. S. S., Hessey S., Hiley C. T., Zaccaria S., Litchfield K., Birkbak N. J., Cadieux E. L., Demeulemeester J., Van Loo P., Adusumilli P. S., Tan K. S., Cheema W., Sanchez-Vega F., Jones D. R., Rekhtman N., Travis W. D., Hackshaw A., Marafioti T., Salgado R., Le Quesne J., Nicholson A. G., Lester J. F., Bajaj A., Nakas A., Sodha-Ramdeen A., Ang K., Tufail M., Chowdhry M. F., Scotland M., Boyles R., Rathinam S., Wilson C., Marrone D., Dulloo S., Fennell D. A., Matharu G., Shaw J. A., Riley J., Primrose L., Boleti E., Cheyne H., Khalil M., Richardson S., Cruickshank T., Price G., Kerr K. M., Benafif S., Gilbert K., Naidu B., Patel A. J., Osman A., Lacson C., Langman G., Shackleford H., Djearaman M., Kadiri S., Middleton G., Leek A., Hodgkinson J. D., Totten N., Montero A., Smith E., Fontaine E., Granato F., Doran H., Novasio J., Rammohan K., Joseph L., Bishop P., Shah R., Moss S., Joshi V., Crosbie P., Gomes F., Brown K., Carter M., Chaturvedi A., Priest L., Oliveira P., Lindsay C. R., Blackhall F. H., Krebs M. G., Summers Y., Clipson A., Tugwood J., Kerr A., Rothwell D. G., Kilgour E., Dive C., Aerts H. J. W. L., Schwarz R. F., Kaufmann T. L., Wilson G. A., Rosenthal R., Szallasi Z., Kisistok J., Sokac M., Diossy M., Bunkum A., Stewart A., Magness A., Rowan A., Karamani A., Chain B., Castignani C., Bailey C., Weeden C. E., Richard C., Pearce D. R., Karagianni D., Levi D., Hoxha E., Nye E., Gronroos E., Galvez-Cancino F., Athanasopoulou F., Kassiotis G., Stavrou G., Mastrokalos G., Lowe H. L., Matos I. G., Goldman J., Reading J. L., Herrero J., Rane J. K., Nicod J., Lam J. M., Hartley J. A., Peggs K. S., Selvaraju K., Thol K., Ng K. W., Chen K., Dijkstra K., Thakkar K., Ensell L., Shah M., Duran M. V., Litovchenko M., Sunderland M. W., Leung M., Escudero M., Angelova M., Tanic M., Sivakumar M., Chervova O., Lucas O., Al-Sawaf O., Prymas P., Hobson P., Pawlik P., Stone R. K., Bentham R., Hynds R. E., Vendramin R., Lopez S., Gamble S., Ung S. K. A., Quezada S. A., Vanloo S., Boeing S., Beck S., Bola S. K., Denner T., Mourikis T. P., Spanswick V., Barbe V., Lu W. -T., Hill W., Liu W. K., Wu Y., Naito Y., Ramsden Z., Veiga C., Royle G., Collins-Fekete C. -A., Fraioli F., Ashford P., Clark T., Forster M. D., Lee S. M., Borg E., Falzon M., Papadatos-Pastos D., Wilson J., Ahmad T., Procter A. J., Ahmed A., Taylor M. N., Nair A., Lawrence D., Patrini D., Navani N., Thakrar R. M., Janes S. M., Hoogenboom E. M., Monk F., Holding J. W., Choudhary J., Bhakhri K., Scarci M., Hayward M., Panagiotopoulos N., Gorman P., Khiroya R., Stephens R. C., Wong Y. N. S., Bandula S., Sharp A., Smith S., Gower N., Dhanda H. K., Chan K., Pilotti C., Leslie R., Grapa A., Zhang H., AbdulJabbar K., Pan X., Yuan Y., Chuter D., MacKenzie M., Chee S., Alzetani A., Cave J., Scarlett L., Richards J., Ingram P., Austin S., Lim E., De Sousa P., Jordan S., Rice A., Raubenheimer H., Bhayani H., Ambrose L., Devaraj A., Chavan H., Begum S., Buderi S. I., Kaniu D., Malima M., Booth S., Fernandes N., Shah P., Proli C., Hewish M., Danson S., Shackcloth M. J., Robinson L., Russell P., Blyth K. G., Dick C., Kirk A., Asif M., Bilancia R., Kostoulas N., Thomas M., McGranahan N., Swanton C., and Jamal-Hanjani M.
Abstract: Lung adenocarcinomas (LUADs) display a broad histological spectrum from low-grade lepidic tumors through to mid-grade acinar and papillary and high-grade solid, cribriform and micropapillary tumors. How morphology reflects tumor evolution and disease progression is poorly understood. Whole-exome sequencing data generated from 805 primary tumor regions and 121 paired metastatic samples across 248 LUADs from the TRACERx 421 cohort, together with RNA-sequencing data from 463 primary tumor regions, were integrated with detailed whole-tumor and regional histopathological analysis. Tumors with predominantly high-grade patterns showed increased chromosomal complexity, with higher burden of loss of heterozygosity and subclonal somatic copy number alterations. Individual regions in predominantly high-grade pattern tumors exhibited higher proliferation and lower clonal diversity, potentially reflecting large recent subclonal expansions. Co-occurrence of truncal loss of chromosomes 3p and 3q was enriched in predominantly low-/mid-grade tumors, while purely undifferentiated solid-pattern tumors had a higher frequency of truncal arm or focal 3q gains and SMARCA4 gene alterations compared with mixed-pattern tumors with a solid component, suggesting distinct evolutionary trajectories. Clonal evolution analysis revealed that tumors tend to evolve toward higher-grade patterns. The presence of micropapillary pattern and ‘tumor spread through air spaces’ were associated with intrathoracic recurrence, in contrast to the presence of solid/cribriform patterns, necrosis and preoperative circulating tumor DNA detection, which were associated with extra-thoracic recurrence. These data provide insights into the relationship between LUAD morphology, the underlying evolutionary genomic landscape, and clinical and anatomical relapse risk.
Published: 2023

27. Genomic–transcriptomic evolution in lung cancer and metastasis

Author: Martinez-Ruiz, C, Black, J, Puttick, C, Hill, M, Demeulemeester, J, Larose Cadieux, E, Thol, K, Jones, T, Veeriah, S, Naceur-Lombardelli, C, Toncheva, A, Prymas, P, Rowan, A, Ward, S, Cubitt, L, Athanasopoulou, F, Pich, O, Karasaki, T, Moore, D, Salgado, R, Colliver, E, Castignani, C, Dietzen, M, Huebner, A, Al Bakir, M, Tanic, M, Watkins, T, Lim, E, Al-Rashed, A, Lang, D, Clements, J, Cook, D, Rosenthal, R, Wilson, G, Frankell, A, de Carne Trecesson, S, East, P, Kanu, N, Litchfield, K, Birkbak, N, Hackshaw, A, Beck, S, Van Loo, P, Jamal-Hanjani, M, Mcgranahan, N, Swanton, C, Bakir, M, Lester, J, Bajaj, A, Nakas, A, Sodha-Ramdeen, A, Ang, K, Tufail, M, Chowdhry, M, Scotland, M, Boyles, R, Rathinam, S, Wilson, C, Marrone, D, Dulloo, S, Fennell, D, Matharu, G, Shaw, J, Riley, J, Primrose, L, Boleti, E, Cheyne, H, Khalil, M, Richardson, S, Cruickshank, T, Price, G, Kerr, K, Benafif, S, Gilbert, K, Naidu, B, Patel, A, Osman, A, Lacson, C, Langman, G, Shackleford, H, Djearaman, M, Kadiri, S, Middleton, G, Leek, A, Hodgkinson, J, Totten, N, Montero, A, Smith, E, Fontaine, E, Granato, F, Doran, H, Novasio, J, Rammohan, K, Joseph, L, Bishop, P, Shah, R, Moss, S, Joshi, V, Crosbie, P, Gomes, F, Brown, K, Carter, M, Chaturvedi, A, Priest, L, Oliveira, P, Lindsay, C, Blackhall, F, Krebs, M, Summers, Y, Clipson, A, Tugwood, J, Kerr, A, Rothwell, D, Kilgour, E, Dive, C, Aerts, H, Schwarz, R, Kaufmann, T, Szallasi, Z, Kisistok, J, Sokac, M, Diossy, M, Bunkum, A, Stewart, A, Magness, A, Karamani, A, Chain, B, Campbell, B, Bailey, C, Abbosh, C, Weeden, C, Lee, C, Richard, C, Hiley, C, Pearce, D, Karagianni, D, Biswas, D, Levi, D, Hoxha, E, Nye, E, Gronroos, E, Galvez-Cancino, F, Gimeno-Valiente, F, Kassiotis, G, Stavrou, G, Mastrokalos, G, Zhai, H, Lowe, H, Matos, I, Goldman, J, Reading, J, Herrero, J, Rane, J, Nicod, J, Lam, J, Hartley, J, Peggs, K, Enfield, K, Selvaraju, K, Ng, K, Chen, K, Dijkstra, K, Grigoriadis, K, Thakkar, K, Ensell, L, Shah, M, Duran, M, Litovchenko, M, Sunderland, M, Leung, M, Escudero, M, Angelova, M, Sivakumar, M, Chervova, O, Lucas, O, Al-Sawaf, O, Hobson, P, Pawlik, P, Stone, R, Bentham, R, Hynds, R, Vendramin, R, Saghafinia, S, Lopez, S, Gamble, S, Ung, S, Quezada, S, Vanloo, S, Zaccaria, S, Hessey, S, Boeing, S, Bola, S, Denner, T, Marafioti, T, Mourikis, T, Spanswick, V, Barbe, V, Lu, W, Hill, W, Liu, W, Wu, Y, Naito, Y, Ramsden, Z, Veiga, C, Royle, G, Collins-Fekete, C, Fraioli, F, Ashford, P, Clark, T, Forster, M, Lee, S, Borg, E, Falzon, M, Papadatos-Pastos, D, Wilson, J, Ahmad, T, Procter, A, Ahmed, A, Taylor, M, Nair, A, Lawrence, D, Patrini, D, Navani, N, Thakrar, R, Janes, S, Hoogenboom, E, Monk, F, Holding, J, Choudhary, J, Bhakhri, K, Scarci, M, Hayward, M, Panagiotopoulos, N, Gorman, P, Khiroya, R, Stephens, R, Wong, Y, Bandula, S, Sharp, A, Smith, S, Gower, N, Dhanda, H, Chan, K, Pilotti, C, Leslie, R, Grapa, A, Zhang, H, Abduljabbar, K, Pan, X, Yuan, Y, Chuter, D, Mackenzie, M, Chee, S, Alzetani, A, Cave, J, Scarlett, L, Richards, J, Ingram, P, Austin, S, De Sousa, P, Jordan, S, Rice, A, Raubenheimer, H, Bhayani, H, Ambrose, L, Devaraj, A, Chavan, H, Begum, S, Buderi, S, Kaniu, D, Malima, M, Booth, S, Nicholson, A, Fernandes, N, Shah, P, Proli, C, Hewish, M, Danson, S, Shackcloth, M, Robinson, L, Russell, P, Blyth, K, Dick, C, Le Quesne, J, Kirk, A, Asif, M, Bilancia, R, Kostoulas, N, Thomas, M, Martinez-Ruiz C., Black J. R. M., Puttick C., Hill M. S., Demeulemeester J., Larose Cadieux E., Thol K., Jones T. P., Veeriah S., Naceur-Lombardelli C., Toncheva A., Prymas P., Rowan A., Ward S., Cubitt L., Athanasopoulou F., Pich O., Karasaki T., Moore D. A., Salgado R., Colliver E., Castignani C., Dietzen M., Huebner A., Al Bakir M., Tanic M., Watkins T. B. K., Lim E. L., Al-Rashed A. M., Lang D., Clements J., Cook D. E., Rosenthal R., Wilson G. A., Frankell A. M., de Carne Trecesson S., East P., Kanu N., Litchfield K., Birkbak N. J., Hackshaw A., Beck S., Van Loo P., Jamal-Hanjani M., McGranahan N., Swanton C., Bakir M. A., Lester J. F., Bajaj A., Nakas A., Sodha-Ramdeen A., Ang K., Tufail M., Chowdhry M. F., Scotland M., Boyles R., Rathinam S., Wilson C., Marrone D., Dulloo S., Fennell D. A., Matharu G., Shaw J. A., Riley J., Primrose L., Boleti E., Cheyne H., Khalil M., Richardson S., Cruickshank T., Price G., Kerr K. M., Benafif S., Gilbert K., Naidu B., Patel A. J., Osman A., Lacson C., Langman G., Shackleford H., Djearaman M., Kadiri S., Middleton G., Leek A., Hodgkinson J. D., Totten N., Montero A., Smith E., Fontaine E., Granato F., Doran H., Novasio J., Rammohan K., Joseph L., Bishop P., Shah R., Moss S., Joshi V., Crosbie P., Gomes F., Brown K., Carter M., Chaturvedi A., Priest L., Oliveira P., Lindsay C. R., Blackhall F. H., Krebs M. G., Summers Y., Clipson A., Tugwood J., Kerr A., Rothwell D. G., Kilgour E., Dive C., Aerts H. J. W. L., Schwarz R. F., Kaufmann T. L., Szallasi Z., Kisistok J., Sokac M., Diossy M., Bunkum A., Stewart A., Magness A., Karamani A., Chain B., Campbell B. B., Bailey C., Abbosh C., Weeden C. E., Lee C., Richard C., Hiley C. T., Pearce D. R., Karagianni D., Biswas D., Levi D., Hoxha E., Nye E., Gronroos E., Galvez-Cancino F., Gimeno-Valiente F., Kassiotis G., Stavrou G., Mastrokalos G., Zhai H., Lowe H. L., Matos I. G., Goldman J., Reading J. L., Herrero J., Rane J. K., Nicod J., Lam J. M., Hartley J. A., Peggs K. S., Enfield K. S. S., Selvaraju K., Ng K. W., Chen K., Dijkstra K., Grigoriadis K., Thakkar K., Ensell L., Shah M., Duran M. V., Litovchenko M., Sunderland M. W., Leung M., Escudero M., Angelova M., Sivakumar M., Chervova O., Lucas O., Al-Sawaf O., Hobson P., Pawlik P., Stone R. K., Bentham R., Hynds R. E., Vendramin R., Saghafinia S., Lopez S., Gamble S., Ung S. K. A., Quezada S. A., Vanloo S., Zaccaria S., Hessey S., Boeing S., Bola S. K., Denner T., Marafioti T., Mourikis T. P., Spanswick V., Barbe V., Lu W. -T., Hill W., Liu W. K., Wu Y., Naito Y., Ramsden Z., Veiga C., Royle G., Collins-Fekete C. -A., Fraioli F., Ashford P., Clark T., Forster M. D., Lee S. M., Borg E., Falzon M., Papadatos-Pastos D., Wilson J., Ahmad T., Procter A. J., Ahmed A., Taylor M. N., Nair A., Lawrence D., Patrini D., Navani N., Thakrar R. M., Janes S. M., Hoogenboom E. M., Monk F., Holding J. W., Choudhary J., Bhakhri K., Scarci M., Hayward M., Panagiotopoulos N., Gorman P., Khiroya R., Stephens R. C. M., Wong Y. N. S., Bandula S., Sharp A., Smith S., Gower N., Dhanda H. K., Chan K., Pilotti C., Leslie R., Grapa A., Zhang H., AbdulJabbar K., Pan X., Yuan Y., Chuter D., MacKenzie M., Chee S., Alzetani A., Cave J., Scarlett L., Richards J., Ingram P., Austin S., Lim E., De Sousa P., Jordan S., Rice A., Raubenheimer H., Bhayani H., Ambrose L., Devaraj A., Chavan H., Begum S., Buderi S. I., Kaniu D., Malima M., Booth S., Nicholson A. G., Fernandes N., Shah P., Proli C., Hewish M., Danson S., Shackcloth M. J., Robinson L., Russell P., Blyth K. G., Dick C., Le Quesne J., Kirk A., Asif M., Bilancia R., Kostoulas N., Thomas M., Martinez-Ruiz, C, Black, J, Puttick, C, Hill, M, Demeulemeester, J, Larose Cadieux, E, Thol, K, Jones, T, Veeriah, S, Naceur-Lombardelli, C, Toncheva, A, Prymas, P, Rowan, A, Ward, S, Cubitt, L, Athanasopoulou, F, Pich, O, Karasaki, T, Moore, D, Salgado, R, Colliver, E, Castignani, C, Dietzen, M, Huebner, A, Al Bakir, M, Tanic, M, Watkins, T, Lim, E, Al-Rashed, A, Lang, D, Clements, J, Cook, D, Rosenthal, R, Wilson, G, Frankell, A, de Carne Trecesson, S, East, P, Kanu, N, Litchfield, K, Birkbak, N, Hackshaw, A, Beck, S, Van Loo, P, Jamal-Hanjani, M, Mcgranahan, N, Swanton, C, Bakir, M, Lester, J, Bajaj, A, Nakas, A, Sodha-Ramdeen, A, Ang, K, Tufail, M, Chowdhry, M, Scotland, M, Boyles, R, Rathinam, S, Wilson, C, Marrone, D, Dulloo, S, Fennell, D, Matharu, G, Shaw, J, Riley, J, Primrose, L, Boleti, E, Cheyne, H, Khalil, M, Richardson, S, Cruickshank, T, Price, G, Kerr, K, Benafif, S, Gilbert, K, Naidu, B, Patel, A, Osman, A, Lacson, C, Langman, G, Shackleford, H, Djearaman, M, Kadiri, S, Middleton, G, Leek, A, Hodgkinson, J, Totten, N, Montero, A, Smith, E, Fontaine, E, Granato, F, Doran, H, Novasio, J, Rammohan, K, Joseph, L, Bishop, P, Shah, R, Moss, S, Joshi, V, Crosbie, P, Gomes, F, Brown, K, Carter, M, Chaturvedi, A, Priest, L, Oliveira, P, Lindsay, C, Blackhall, F, Krebs, M, Summers, Y, Clipson, A, Tugwood, J, Kerr, A, Rothwell, D, Kilgour, E, Dive, C, Aerts, H, Schwarz, R, Kaufmann, T, Szallasi, Z, Kisistok, J, Sokac, M, Diossy, M, Bunkum, A, Stewart, A, Magness, A, Karamani, A, Chain, B, Campbell, B, Bailey, C, Abbosh, C, Weeden, C, Lee, C, Richard, C, Hiley, C, Pearce, D, Karagianni, D, Biswas, D, Levi, D, Hoxha, E, Nye, E, Gronroos, E, Galvez-Cancino, F, Gimeno-Valiente, F, Kassiotis, G, Stavrou, G, Mastrokalos, G, Zhai, H, Lowe, H, Matos, I, Goldman, J, Reading, J, Herrero, J, Rane, J, Nicod, J, Lam, J, Hartley, J, Peggs, K, Enfield, K, Selvaraju, K, Ng, K, Chen, K, Dijkstra, K, Grigoriadis, K, Thakkar, K, Ensell, L, Shah, M, Duran, M, Litovchenko, M, Sunderland, M, Leung, M, Escudero, M, Angelova, M, Sivakumar, M, Chervova, O, Lucas, O, Al-Sawaf, O, Hobson, P, Pawlik, P, Stone, R, Bentham, R, Hynds, R, Vendramin, R, Saghafinia, S, Lopez, S, Gamble, S, Ung, S, Quezada, S, Vanloo, S, Zaccaria, S, Hessey, S, Boeing, S, Bola, S, Denner, T, Marafioti, T, Mourikis, T, Spanswick, V, Barbe, V, Lu, W, Hill, W, Liu, W, Wu, Y, Naito, Y, Ramsden, Z, Veiga, C, Royle, G, Collins-Fekete, C, Fraioli, F, Ashford, P, Clark, T, Forster, M, Lee, S, Borg, E, Falzon, M, Papadatos-Pastos, D, Wilson, J, Ahmad, T, Procter, A, Ahmed, A, Taylor, M, Nair, A, Lawrence, D, Patrini, D, Navani, N, Thakrar, R, Janes, S, Hoogenboom, E, Monk, F, Holding, J, Choudhary, J, Bhakhri, K, Scarci, M, Hayward, M, Panagiotopoulos, N, Gorman, P, Khiroya, R, Stephens, R, Wong, Y, Bandula, S, Sharp, A, Smith, S, Gower, N, Dhanda, H, Chan, K, Pilotti, C, Leslie, R, Grapa, A, Zhang, H, Abduljabbar, K, Pan, X, Yuan, Y, Chuter, D, Mackenzie, M, Chee, S, Alzetani, A, Cave, J, Scarlett, L, Richards, J, Ingram, P, Austin, S, De Sousa, P, Jordan, S, Rice, A, Raubenheimer, H, Bhayani, H, Ambrose, L, Devaraj, A, Chavan, H, Begum, S, Buderi, S, Kaniu, D, Malima, M, Booth, S, Nicholson, A, Fernandes, N, Shah, P, Proli, C, Hewish, M, Danson, S, Shackcloth, M, Robinson, L, Russell, P, Blyth, K, Dick, C, Le Quesne, J, Kirk, A, Asif, M, Bilancia, R, Kostoulas, N, Thomas, M, Martinez-Ruiz C., Black J. R. M., Puttick C., Hill M. S., Demeulemeester J., Larose Cadieux E., Thol K., Jones T. P., Veeriah S., Naceur-Lombardelli C., Toncheva A., Prymas P., Rowan A., Ward S., Cubitt L., Athanasopoulou F., Pich O., Karasaki T., Moore D. A., Salgado R., Colliver E., Castignani C., Dietzen M., Huebner A., Al Bakir M., Tanic M., Watkins T. B. K., Lim E. L., Al-Rashed A. M., Lang D., Clements J., Cook D. E., Rosenthal R., Wilson G. A., Frankell A. M., de Carne Trecesson S., East P., Kanu N., Litchfield K., Birkbak N. J., Hackshaw A., Beck S., Van Loo P., Jamal-Hanjani M., McGranahan N., Swanton C., Bakir M. A., Lester J. F., Bajaj A., Nakas A., Sodha-Ramdeen A., Ang K., Tufail M., Chowdhry M. F., Scotland M., Boyles R., Rathinam S., Wilson C., Marrone D., Dulloo S., Fennell D. A., Matharu G., Shaw J. A., Riley J., Primrose L., Boleti E., Cheyne H., Khalil M., Richardson S., Cruickshank T., Price G., Kerr K. M., Benafif S., Gilbert K., Naidu B., Patel A. J., Osman A., Lacson C., Langman G., Shackleford H., Djearaman M., Kadiri S., Middleton G., Leek A., Hodgkinson J. D., Totten N., Montero A., Smith E., Fontaine E., Granato F., Doran H., Novasio J., Rammohan K., Joseph L., Bishop P., Shah R., Moss S., Joshi V., Crosbie P., Gomes F., Brown K., Carter M., Chaturvedi A., Priest L., Oliveira P., Lindsay C. R., Blackhall F. H., Krebs M. G., Summers Y., Clipson A., Tugwood J., Kerr A., Rothwell D. G., Kilgour E., Dive C., Aerts H. J. W. L., Schwarz R. F., Kaufmann T. L., Szallasi Z., Kisistok J., Sokac M., Diossy M., Bunkum A., Stewart A., Magness A., Karamani A., Chain B., Campbell B. B., Bailey C., Abbosh C., Weeden C. E., Lee C., Richard C., Hiley C. T., Pearce D. R., Karagianni D., Biswas D., Levi D., Hoxha E., Nye E., Gronroos E., Galvez-Cancino F., Gimeno-Valiente F., Kassiotis G., Stavrou G., Mastrokalos G., Zhai H., Lowe H. L., Matos I. G., Goldman J., Reading J. L., Herrero J., Rane J. K., Nicod J., Lam J. M., Hartley J. A., Peggs K. S., Enfield K. S. S., Selvaraju K., Ng K. W., Chen K., Dijkstra K., Grigoriadis K., Thakkar K., Ensell L., Shah M., Duran M. V., Litovchenko M., Sunderland M. W., Leung M., Escudero M., Angelova M., Sivakumar M., Chervova O., Lucas O., Al-Sawaf O., Hobson P., Pawlik P., Stone R. K., Bentham R., Hynds R. E., Vendramin R., Saghafinia S., Lopez S., Gamble S., Ung S. K. A., Quezada S. A., Vanloo S., Zaccaria S., Hessey S., Boeing S., Bola S. K., Denner T., Marafioti T., Mourikis T. P., Spanswick V., Barbe V., Lu W. -T., Hill W., Liu W. K., Wu Y., Naito Y., Ramsden Z., Veiga C., Royle G., Collins-Fekete C. -A., Fraioli F., Ashford P., Clark T., Forster M. D., Lee S. M., Borg E., Falzon M., Papadatos-Pastos D., Wilson J., Ahmad T., Procter A. J., Ahmed A., Taylor M. N., Nair A., Lawrence D., Patrini D., Navani N., Thakrar R. M., Janes S. M., Hoogenboom E. M., Monk F., Holding J. W., Choudhary J., Bhakhri K., Scarci M., Hayward M., Panagiotopoulos N., Gorman P., Khiroya R., Stephens R. C. M., Wong Y. N. S., Bandula S., Sharp A., Smith S., Gower N., Dhanda H. K., Chan K., Pilotti C., Leslie R., Grapa A., Zhang H., AbdulJabbar K., Pan X., Yuan Y., Chuter D., MacKenzie M., Chee S., Alzetani A., Cave J., Scarlett L., Richards J., Ingram P., Austin S., Lim E., De Sousa P., Jordan S., Rice A., Raubenheimer H., Bhayani H., Ambrose L., Devaraj A., Chavan H., Begum S., Buderi S. I., Kaniu D., Malima M., Booth S., Nicholson A. G., Fernandes N., Shah P., Proli C., Hewish M., Danson S., Shackcloth M. J., Robinson L., Russell P., Blyth K. G., Dick C., Le Quesne J., Kirk A., Asif M., Bilancia R., Kostoulas N., and Thomas M.
Abstract: Intratumour heterogeneity (ITH) fuels lung cancer evolution, which leads to immune evasion and resistance to therapy1. Here, using paired whole-exome and RNA sequencing data, we investigate intratumour transcriptomic diversity in 354 non-small cell lung cancer tumours from 347 out of the first 421 patients prospectively recruited into the TRACERx study2,3. Analyses of 947 tumour regions, representing both primary and metastatic disease, alongside 96 tumour-adjacent normal tissue samples implicate the transcriptome as a major source of phenotypic variation. Gene expression levels and ITH relate to patterns of positive and negative selection during tumour evolution. We observe frequent copy number-independent allele-specific expression that is linked to epigenomic dysfunction. Allele-specific expression can also result in genomic–transcriptomic parallel evolution, which converges on cancer gene disruption. We extract signatures of RNA single-base substitutions and link their aetiology to the activity of the RNA-editing enzymes ADAR and APOBEC3A, thereby revealing otherwise undetected ongoing APOBEC activity in tumours. Characterizing the transcriptomes of primary–metastatic tumour pairs, we combine multiple machine-learning approaches that leverage genomic and transcriptomic variables to link metastasis-seeding potential to the evolutionary context of mutations and increased proliferation within primary tumour regions. These results highlight the interplay between the genome and transcriptome in influencing ITH, lung cancer evolution and metastasis.
Published: 2023

28. Tracking early lung cancer metastatic dissemination in TRACERx using ctDNA

Author: Abbosh, C, Frankell, A, Harrison, T, Kisistok, J, Garnett, A, Johnson, L, Veeriah, S, Moreau, M, Chesh, A, Chaunzwa, T, Weiss, J, Schroeder, M, Ward, S, Grigoriadis, K, Shahpurwalla, A, Litchfield, K, Puttick, C, Biswas, D, Karasaki, T, Black, J, Martinez-Ruiz, C, Bakir, M, Pich, O, Watkins, T, Lim, E, Huebner, A, Moore, D, Godin-Heymann, N, L'Hernault, A, Bye, H, Odell, A, Roberts, P, Gomes, F, Patel, A, Manzano, E, Hiley, C, Carey, N, Riley, J, Cook, D, Hodgson, D, Stetson, D, Barrett, J, Kortlever, R, Evan, G, Hackshaw, A, Daber, R, Shaw, J, Aerts, H, Licon, A, Stahl, J, Jamal-Hanjani, M, Lester, J, Bajaj, A, Nakas, A, Sodha-Ramdeen, A, Ang, K, Tufail, M, Chowdhry, M, Scotland, M, Boyles, R, Rathinam, S, Wilson, C, Marrone, D, Dulloo, S, Fennell, D, Matharu, G, Primrose, L, Boleti, E, Cheyne, H, Khalil, M, Richardson, S, Cruickshank, T, Price, G, Kerr, K, Benafif, S, Gilbert, K, Naidu, B, Osman, A, Lacson, C, Langman, G, Shackleford, H, Djearaman, M, Kadiri, S, Middleton, G, Leek, A, Hodgkinson, J, Totten, N, Montero, A, Smith, E, Fontaine, E, Granato, F, Doran, H, Novasio, J, Rammohan, K, Joseph, L, Bishop, P, Shah, R, Moss, S, Joshi, V, Crosbie, P, Brown, K, Carter, M, Chaturvedi, A, Priest, L, Oliveira, P, Lindsay, C, Blackhall, F, Krebs, M, Summers, Y, Clipson, A, Tugwood, J, Kerr, A, Rothwell, D, Kilgour, E, Dive, C, Schwarz, R, Kaufmann, T, Wilson, G, Rosenthal, R, Van Loo, P, Szallasi, Z, Sokac, M, Salgado, R, Diossy, M, Demeulemeester, J, Bunkum, A, Stewart, A, Magness, A, Rowan, A, Karamani, A, Toncheva, A, Chain, B, Campbell, B, Castignani, C, Bailey, C, Weeden, C, Lee, C, Richard, C, Naceur-Lombardelli, C, Pearce, D, Karagianni, D, Levi, D, Hoxha, E, Larose Cadieux, E, Colliver, E, Nye, E, Gronroos, E, Galvez-Cancino, F, Athanasopoulou, F, Gimeno-Valiente, F, Kassiotis, G, Stavrou, G, Mastrokalos, G, Zhai, H, Lowe, H, Matos, I, Goldman, J, Reading, J, Herrero, J, Rane, J, Nicod, J, Lam, J, Hartley, J, Peggs, K, Enfield, K, Selvaraju, K, Thol, K, Ng, K, Chen, K, Dijkstra, K, Thakkar, K, Ensell, L, Shah, M, Vasquez, M, Litovchenko, M, Werner Sunderland, M, Hill, M, Dietzen, M, Leung, M, Escudero, M, Angelova, M, Tanic, M, Sivakumar, M, Kanu, N, Chervova, O, Lucas, O, Al-Sawaf, O, Prymas, P, Hobson, P, Pawlik, P, Stone, R, Bentham, R, Hynds, R, Vendramin, R, Saghafinia, S, Lopez, S, Gamble, S, Ung, S, Quezada, S, Vanloo, S, Zaccaria, S, Hessey, S, Boeing, S, Beck, S, Bola, S, Denner, T, Marafioti, T, Mourikis, T, Spanswick, V, Barbe, V, Lu, W, Hill, W, Liu, W, Wu, Y, Naito, Y, Ramsden, Z, Veiga, C, Royle, G, Collins-Fekete, C, Fraioli, F, Ashford, P, Clark, T, Forster, M, Lee, S, Borg, E, Falzon, M, Papadatos-Pastos, D, Wilson, J, Ahmad, T, Procter, A, Ahmed, A, Taylor, M, Nair, A, Lawrence, D, Patrini, D, Navani, N, Thakrar, R, Janes, S, Martinoni Hoogenboom, E, Monk, F, Holding, J, Choudhary, J, Bhakhri, K, Scarci, M, Hayward, M, Panagiotopoulos, N, Gorman, P, Khiroya, R, Stephens, R, Wong, Y, Bandula, S, Sharp, A, Smith, S, Gower, N, Dhanda, H, Chan, K, Pilotti, C, Leslie, R, Grapa, A, Zhang, H, Abduljabbar, K, Pan, X, Yuan, Y, Chuter, D, Mackenzie, M, Chee, S, Alzetani, A, Cave, J, Scarlett, L, Richards, J, Ingram, P, Austin, S, De Sousa, P, Jordan, S, Rice, A, Raubenheimer, H, Bhayani, H, Ambrose, L, Devaraj, A, Chavan, H, Begum, S, Buderi, S, Kaniu, D, Malima, M, Booth, S, Nicholson, A, Fernandes, N, Shah, P, Proli, C, Hewish, M, Danson, S, Shackcloth, M, Robinson, L, Russell, P, Blyth, K, Dick, C, Le Quesne, J, Kirk, A, Asif, M, Bilancia, R, Kostoulas, N, Thomas, M, Birkbak, N, Mcgranahan, N, Swanton, C, Abbosh C., Frankell A. M., Harrison T., Kisistok J., Garnett A., Johnson L., Veeriah S., Moreau M., Chesh A., Chaunzwa T. L., Weiss J., Schroeder M. R., Ward S., Grigoriadis K., Shahpurwalla A., Litchfield K., Puttick C., Biswas D., Karasaki T., Black J. R. M., Martinez-Ruiz C., Bakir M. A., Pich O., Watkins T. B. K., Lim E. L., Huebner A., Moore D. A., Godin-Heymann N., L'Hernault A., Bye H., Odell A., Roberts P., Gomes F., Patel A. J., Manzano E., Hiley C. T., Carey N., Riley J., Cook D. E., Hodgson D., Stetson D., Barrett J. C., Kortlever R. M., Evan G. I., Hackshaw A., Daber R. D., Shaw J. A., Aerts H. J. W. L., Licon A., Stahl J., Jamal-Hanjani M., Lester J. F., Bajaj A., Nakas A., Sodha-Ramdeen A., Ang K., Tufail M., Chowdhry M. F., Scotland M., Boyles R., Rathinam S., Wilson C., Marrone D., Dulloo S., Fennell D. A., Matharu G., Primrose L., Boleti E., Cheyne H., Khalil M., Richardson S., Cruickshank T., Price G., Kerr K. M., Benafif S., Gilbert K., Naidu B., Osman A., Lacson C., Langman G., Shackleford H., Djearaman M., Kadiri S., Middleton G., Leek A., Hodgkinson J. D., Totten N., Montero A., Smith E., Fontaine E., Granato F., Doran H., Novasio J., Rammohan K., Joseph L., Bishop P., Shah R., Moss S., Joshi V., Crosbie P., Brown K., Carter M., Chaturvedi A., Priest L., Oliveira P., Lindsay C. R., Blackhall F. H., Krebs M. G., Summers Y., Clipson A., Tugwood J., Kerr A., Rothwell D. G., Kilgour E., Dive C., Schwarz R. F., Kaufmann T. L., Wilson G. A., Rosenthal R., Van Loo P., Szallasi Z., Sokac M., Salgado R., Diossy M., Demeulemeester J., Bunkum A., Stewart A., Magness A., Rowan A., Karamani A., Toncheva A., Chain B., Campbell B. B., Castignani C., Bailey C., Weeden C. E., Lee C., Richard C., Naceur-Lombardelli C., Pearce D. R., Karagianni D., Levi D., Hoxha E., Larose Cadieux E., Colliver E., Nye E., Gronroos E., Galvez-Cancino F., Athanasopoulou F., Gimeno-Valiente F., Kassiotis G., Stavrou G., Mastrokalos G., Zhai H., Lowe H. L., Matos I., Goldman J., Reading J. L., Herrero J., Rane J. K., Nicod J., Lam J. M., Hartley J. A., Peggs K. S., Enfield K. S. S., Selvaraju K., Thol K., Ng K. W., Chen K., Dijkstra K., Thakkar K., Ensell L., Shah M., Vasquez M., Litovchenko M., Werner Sunderland M., Hill M. S., Dietzen M., Leung M., Escudero M., Angelova M., Tanic M., Sivakumar M., Kanu N., Chervova O., Lucas O., Al-Sawaf O., Prymas P., Hobson P., Pawlik P., Stone R. K., Bentham R., Hynds R. E., Vendramin R., Saghafinia S., Lopez S., Gamble S., Ung S. K. A., Quezada S. A., Vanloo S., Zaccaria S., Hessey S., Boeing S., Beck S., Bola S. K., Denner T., Marafioti T., Mourikis T. P., Spanswick V., Barbe V., Lu W. -T., Hill W., Liu W. K., Wu Y., Naito Y., Ramsden Z., Veiga C., Royle G., Collins-Fekete C. -A., Fraioli F., Ashford P., Clark T., Forster M. D., Lee S. M., Borg E., Falzon M., Papadatos-Pastos D., Wilson J., Ahmad T., Procter A. J., Ahmed A., Taylor M. N., Nair A., Lawrence D., Patrini D., Navani N., Thakrar R. M., Janes S. M., Martinoni Hoogenboom E., Monk F., Holding J. W., Choudhary J., Bhakhri K., Scarci M., Hayward M., Panagiotopoulos N., Gorman P., Khiroya R., Stephens R. C., Wong Y. N. S., Bandula S., Sharp A., Smith S., Gower N., Dhanda H. K., Chan K., Pilotti C., Leslie R., Grapa A., Zhang H., AbdulJabbar K., Pan X., Yuan Y., Chuter D., MacKenzie M., Chee S., Alzetani A., Cave J., Scarlett L., Richards J., Ingram P., Austin S., Lim E., De Sousa P., Jordan S., Rice A., Raubenheimer H., Bhayani H., Ambrose L., Devaraj A., Chavan H., Begum S., Buderi S. I., Kaniu D., Malima M., Booth S., Nicholson A. G., Fernandes N., Shah P., Proli C., Hewish M., Danson S., Shackcloth M. J., Robinson L., Russell P., Blyth K. G., Dick C., Le Quesne J., Kirk A., Asif M., Bilancia R., Kostoulas N., Thomas M., Birkbak N. J., McGranahan N., Swanton C., Abbosh, C, Frankell, A, Harrison, T, Kisistok, J, Garnett, A, Johnson, L, Veeriah, S, Moreau, M, Chesh, A, Chaunzwa, T, Weiss, J, Schroeder, M, Ward, S, Grigoriadis, K, Shahpurwalla, A, Litchfield, K, Puttick, C, Biswas, D, Karasaki, T, Black, J, Martinez-Ruiz, C, Bakir, M, Pich, O, Watkins, T, Lim, E, Huebner, A, Moore, D, Godin-Heymann, N, L'Hernault, A, Bye, H, Odell, A, Roberts, P, Gomes, F, Patel, A, Manzano, E, Hiley, C, Carey, N, Riley, J, Cook, D, Hodgson, D, Stetson, D, Barrett, J, Kortlever, R, Evan, G, Hackshaw, A, Daber, R, Shaw, J, Aerts, H, Licon, A, Stahl, J, Jamal-Hanjani, M, Lester, J, Bajaj, A, Nakas, A, Sodha-Ramdeen, A, Ang, K, Tufail, M, Chowdhry, M, Scotland, M, Boyles, R, Rathinam, S, Wilson, C, Marrone, D, Dulloo, S, Fennell, D, Matharu, G, Primrose, L, Boleti, E, Cheyne, H, Khalil, M, Richardson, S, Cruickshank, T, Price, G, Kerr, K, Benafif, S, Gilbert, K, Naidu, B, Osman, A, Lacson, C, Langman, G, Shackleford, H, Djearaman, M, Kadiri, S, Middleton, G, Leek, A, Hodgkinson, J, Totten, N, Montero, A, Smith, E, Fontaine, E, Granato, F, Doran, H, Novasio, J, Rammohan, K, Joseph, L, Bishop, P, Shah, R, Moss, S, Joshi, V, Crosbie, P, Brown, K, Carter, M, Chaturvedi, A, Priest, L, Oliveira, P, Lindsay, C, Blackhall, F, Krebs, M, Summers, Y, Clipson, A, Tugwood, J, Kerr, A, Rothwell, D, Kilgour, E, Dive, C, Schwarz, R, Kaufmann, T, Wilson, G, Rosenthal, R, Van Loo, P, Szallasi, Z, Sokac, M, Salgado, R, Diossy, M, Demeulemeester, J, Bunkum, A, Stewart, A, Magness, A, Rowan, A, Karamani, A, Toncheva, A, Chain, B, Campbell, B, Castignani, C, Bailey, C, Weeden, C, Lee, C, Richard, C, Naceur-Lombardelli, C, Pearce, D, Karagianni, D, Levi, D, Hoxha, E, Larose Cadieux, E, Colliver, E, Nye, E, Gronroos, E, Galvez-Cancino, F, Athanasopoulou, F, Gimeno-Valiente, F, Kassiotis, G, Stavrou, G, Mastrokalos, G, Zhai, H, Lowe, H, Matos, I, Goldman, J, Reading, J, Herrero, J, Rane, J, Nicod, J, Lam, J, Hartley, J, Peggs, K, Enfield, K, Selvaraju, K, Thol, K, Ng, K, Chen, K, Dijkstra, K, Thakkar, K, Ensell, L, Shah, M, Vasquez, M, Litovchenko, M, Werner Sunderland, M, Hill, M, Dietzen, M, Leung, M, Escudero, M, Angelova, M, Tanic, M, Sivakumar, M, Kanu, N, Chervova, O, Lucas, O, Al-Sawaf, O, Prymas, P, Hobson, P, Pawlik, P, Stone, R, Bentham, R, Hynds, R, Vendramin, R, Saghafinia, S, Lopez, S, Gamble, S, Ung, S, Quezada, S, Vanloo, S, Zaccaria, S, Hessey, S, Boeing, S, Beck, S, Bola, S, Denner, T, Marafioti, T, Mourikis, T, Spanswick, V, Barbe, V, Lu, W, Hill, W, Liu, W, Wu, Y, Naito, Y, Ramsden, Z, Veiga, C, Royle, G, Collins-Fekete, C, Fraioli, F, Ashford, P, Clark, T, Forster, M, Lee, S, Borg, E, Falzon, M, Papadatos-Pastos, D, Wilson, J, Ahmad, T, Procter, A, Ahmed, A, Taylor, M, Nair, A, Lawrence, D, Patrini, D, Navani, N, Thakrar, R, Janes, S, Martinoni Hoogenboom, E, Monk, F, Holding, J, Choudhary, J, Bhakhri, K, Scarci, M, Hayward, M, Panagiotopoulos, N, Gorman, P, Khiroya, R, Stephens, R, Wong, Y, Bandula, S, Sharp, A, Smith, S, Gower, N, Dhanda, H, Chan, K, Pilotti, C, Leslie, R, Grapa, A, Zhang, H, Abduljabbar, K, Pan, X, Yuan, Y, Chuter, D, Mackenzie, M, Chee, S, Alzetani, A, Cave, J, Scarlett, L, Richards, J, Ingram, P, Austin, S, De Sousa, P, Jordan, S, Rice, A, Raubenheimer, H, Bhayani, H, Ambrose, L, Devaraj, A, Chavan, H, Begum, S, Buderi, S, Kaniu, D, Malima, M, Booth, S, Nicholson, A, Fernandes, N, Shah, P, Proli, C, Hewish, M, Danson, S, Shackcloth, M, Robinson, L, Russell, P, Blyth, K, Dick, C, Le Quesne, J, Kirk, A, Asif, M, Bilancia, R, Kostoulas, N, Thomas, M, Birkbak, N, Mcgranahan, N, Swanton, C, Abbosh C., Frankell A. M., Harrison T., Kisistok J., Garnett A., Johnson L., Veeriah S., Moreau M., Chesh A., Chaunzwa T. L., Weiss J., Schroeder M. R., Ward S., Grigoriadis K., Shahpurwalla A., Litchfield K., Puttick C., Biswas D., Karasaki T., Black J. R. M., Martinez-Ruiz C., Bakir M. A., Pich O., Watkins T. B. K., Lim E. L., Huebner A., Moore D. A., Godin-Heymann N., L'Hernault A., Bye H., Odell A., Roberts P., Gomes F., Patel A. J., Manzano E., Hiley C. T., Carey N., Riley J., Cook D. E., Hodgson D., Stetson D., Barrett J. C., Kortlever R. M., Evan G. I., Hackshaw A., Daber R. D., Shaw J. A., Aerts H. J. W. L., Licon A., Stahl J., Jamal-Hanjani M., Lester J. F., Bajaj A., Nakas A., Sodha-Ramdeen A., Ang K., Tufail M., Chowdhry M. F., Scotland M., Boyles R., Rathinam S., Wilson C., Marrone D., Dulloo S., Fennell D. A., Matharu G., Primrose L., Boleti E., Cheyne H., Khalil M., Richardson S., Cruickshank T., Price G., Kerr K. M., Benafif S., Gilbert K., Naidu B., Osman A., Lacson C., Langman G., Shackleford H., Djearaman M., Kadiri S., Middleton G., Leek A., Hodgkinson J. D., Totten N., Montero A., Smith E., Fontaine E., Granato F., Doran H., Novasio J., Rammohan K., Joseph L., Bishop P., Shah R., Moss S., Joshi V., Crosbie P., Brown K., Carter M., Chaturvedi A., Priest L., Oliveira P., Lindsay C. R., Blackhall F. H., Krebs M. G., Summers Y., Clipson A., Tugwood J., Kerr A., Rothwell D. G., Kilgour E., Dive C., Schwarz R. F., Kaufmann T. L., Wilson G. A., Rosenthal R., Van Loo P., Szallasi Z., Sokac M., Salgado R., Diossy M., Demeulemeester J., Bunkum A., Stewart A., Magness A., Rowan A., Karamani A., Toncheva A., Chain B., Campbell B. B., Castignani C., Bailey C., Weeden C. E., Lee C., Richard C., Naceur-Lombardelli C., Pearce D. R., Karagianni D., Levi D., Hoxha E., Larose Cadieux E., Colliver E., Nye E., Gronroos E., Galvez-Cancino F., Athanasopoulou F., Gimeno-Valiente F., Kassiotis G., Stavrou G., Mastrokalos G., Zhai H., Lowe H. L., Matos I., Goldman J., Reading J. L., Herrero J., Rane J. K., Nicod J., Lam J. M., Hartley J. A., Peggs K. S., Enfield K. S. S., Selvaraju K., Thol K., Ng K. W., Chen K., Dijkstra K., Thakkar K., Ensell L., Shah M., Vasquez M., Litovchenko M., Werner Sunderland M., Hill M. S., Dietzen M., Leung M., Escudero M., Angelova M., Tanic M., Sivakumar M., Kanu N., Chervova O., Lucas O., Al-Sawaf O., Prymas P., Hobson P., Pawlik P., Stone R. K., Bentham R., Hynds R. E., Vendramin R., Saghafinia S., Lopez S., Gamble S., Ung S. K. A., Quezada S. A., Vanloo S., Zaccaria S., Hessey S., Boeing S., Beck S., Bola S. K., Denner T., Marafioti T., Mourikis T. P., Spanswick V., Barbe V., Lu W. -T., Hill W., Liu W. K., Wu Y., Naito Y., Ramsden Z., Veiga C., Royle G., Collins-Fekete C. -A., Fraioli F., Ashford P., Clark T., Forster M. D., Lee S. M., Borg E., Falzon M., Papadatos-Pastos D., Wilson J., Ahmad T., Procter A. J., Ahmed A., Taylor M. N., Nair A., Lawrence D., Patrini D., Navani N., Thakrar R. M., Janes S. M., Martinoni Hoogenboom E., Monk F., Holding J. W., Choudhary J., Bhakhri K., Scarci M., Hayward M., Panagiotopoulos N., Gorman P., Khiroya R., Stephens R. C., Wong Y. N. S., Bandula S., Sharp A., Smith S., Gower N., Dhanda H. K., Chan K., Pilotti C., Leslie R., Grapa A., Zhang H., AbdulJabbar K., Pan X., Yuan Y., Chuter D., MacKenzie M., Chee S., Alzetani A., Cave J., Scarlett L., Richards J., Ingram P., Austin S., Lim E., De Sousa P., Jordan S., Rice A., Raubenheimer H., Bhayani H., Ambrose L., Devaraj A., Chavan H., Begum S., Buderi S. I., Kaniu D., Malima M., Booth S., Nicholson A. G., Fernandes N., Shah P., Proli C., Hewish M., Danson S., Shackcloth M. J., Robinson L., Russell P., Blyth K. G., Dick C., Le Quesne J., Kirk A., Asif M., Bilancia R., Kostoulas N., Thomas M., Birkbak N. J., McGranahan N., and Swanton C.
Abstract: Circulating tumour DNA (ctDNA) can be used to detect and profile residual tumour cells persisting after curative intent therapy1. The study of large patient cohorts incorporating longitudinal plasma sampling and extended follow-up is required to determine the role of ctDNA as a phylogenetic biomarker of relapse in early-stage non-small-cell lung cancer (NSCLC). Here we developed ctDNA methods tracking a median of 200 mutations identified in resected NSCLC tissue across 1,069 plasma samples collected from 197 patients enrolled in the TRACERx study2. A lack of preoperative ctDNA detection distinguished biologically indolent lung adenocarcinoma with good clinical outcome. Postoperative plasma analyses were interpreted within the context of standard-of-care radiological surveillance and administration of cytotoxic adjuvant therapy. Landmark analyses of plasma samples collected within 120 days after surgery revealed ctDNA detection in 25% of patients, including 49% of all patients who experienced clinical relapse; 3 to 6 monthly ctDNA surveillance identified impending disease relapse in an additional 20% of landmark-negative patients. We developed a bioinformatic tool (ECLIPSE) for non-invasive tracking of subclonal architecture at low ctDNA levels. ECLIPSE identified patients with polyclonal metastatic dissemination, which was associated with a poor clinical outcome. By measuring subclone cancer cell fractions in preoperative plasma, we found that subclones seeding future metastases were significantly more expanded compared with non-metastatic subclones. Our findings will support (neo)adjuvant trial advances and provide insights into the process of metastatic dissemination using low-ctDNA-level liquid biopsy.
Published: 2023

29. Antibodies against endogenous retroviruses promote lung cancer immunotherapy

Author: Ng, K, Boumelha, J, Enfield, K, Almagro, J, Cha, H, Pich, O, Karasaki, T, Moore, D, Salgado, R, Sivakumar, M, Young, G, Molina-Arcas, M, de Carne Trecesson, S, Anastasiou, P, Fendler, A, Au, L, Shepherd, S, Martinez-Ruiz, C, Puttick, C, Black, J, Watkins, T, Kim, H, Shim, S, Faulkner, N, Attig, J, Veeriah, S, Magno, N, Ward, S, Frankell, A, Al Bakir, M, Lim, E, Hill, M, Wilson, G, Cook, D, Birkbak, N, Behrens, A, Yousaf, N, Popat, S, Hackshaw, A, Rowan, A, Huebner, A, Campbell, B, Bailey, C, Lee, C, Biswas, D, Colliver, E, Athanasopoulou, F, Zhai, H, Rane, J, Grigoriadis, K, Dietzen, M, Leung, M, Angelova, M, Lucas, O, Al-Sawaf, O, Rosenthal, R, Nicod, J, Bunkum, A, Toncheva, A, Abbosh, C, Richard, C, Naceur-Lombardelli, C, Gimeno-Valiente, F, Lam, J, Thol, K, Thakkar, K, Werner Sunderland, M, Forster, M, Kanu, N, Prymas, P, Bentham, R, Saghafinia, S, Quezada, S, Vanloo, S, Zaccaria, S, Lee, S, Hessey, S, Liu, W, Papadatos-Pastos, D, Wilson, J, Benafif, S, Ahmad, T, Borg, E, Falzon, M, Khiroya, R, Marafioti, T, Sharp, A, Pilotti, C, Dhanda, H, Chan, K, Gower, N, Leslie, R, Smith, S, Nicholson, A, Herrero, J, Castignani, C, Larose Cadieux, E, Demeulemeester, J, Van Loo, P, Peggs, K, Veiga, C, Royle, G, Collins-Fekete, C, Procter, A, Nair, A, Ahmed, A, Taylor, M, Navani, N, Thakrar, R, Lawrence, D, Patrini, D, Nye, E, Stone, R, Chuter, D, Mackenzie, M, Fraioli, F, Ashford, P, Janes, S, Tanic, M, Beck, S, Rice, A, Devaraj, A, Proli, C, Kaniu, D, Bhayani, H, Chavan, H, Raubenheimer, H, Ambrose, L, Malima, M, Fernandes, N, De Sousa, P, Shah, P, Booth, S, Buderi, S, Jordan, S, Begum, S, Boleti, E, Stewart, A, Magness, A, Weeden, C, Levi, D, Gronroos, E, Goldman, J, Escudero, M, Hobson, P, Vendramin, R, Boeing, S, Denner, T, Barbe, V, Lu, W, Hill, W, Naito, Y, Ramsden, Z, Grapa, A, Zhang, H, Abduljabbar, K, Pan, X, Gilbert, K, Karamani, A, Chain, B, Pearce, D, Karagianni, D, Hoxha, E, Galvez-Cancino, F, Stavrou, G, Mastrokalos, G, Lowe, H, Matos, I, Reading, J, Hartley, J, Selvaraju, K, Chen, K, Ensell, L, Shah, M, Vasquez, M, Litovchenko, M, Chervova, O, Pawlik, P, Hynds, R, Lopez, S, Gamble, S, Ung, S, Bola, S, Mourikis, T, Spanswick, V, Wu, Y, Martinoni Hoogenboom, E, Monk, F, Holding, J, Choudhary, J, Bhakhri, K, Scarci, M, Hayward, M, Panagiotopoulos, N, Gorman, P, Stephens, R, Bandula, S, Wong, Y, Clark, T, Cheyne, H, Khalil, M, Richardson, S, Cruickshank, T, Naidu, B, Matharu, G, Shaw, J, Riley, J, Primrose, L, Le Quesne, J, Blyth, K, Kerr, A, Clipson, A, Chaturvedi, A, Dive, C, Rothwell, D, Kilgour, E, Tugwood, J, Priest, L, Oliveira, P, Crosbie, P, Price, G, Cave, J, Kerr, K, Lindsay, C, Blackhall, F, Krebs, M, Summers, Y, Kirk, A, Thomas, M, Asif, M, Kostoulas, N, Bilancia, R, Middleton, G, Shackcloth, M, Leek, A, Hodgkinson, J, Totten, N, Dick, C, Robinson, L, Russell, P, Hewish, M, Danson, S, Lester, J, Gomes, F, Brown, K, Carter, M, Patel, A, Osman, A, Lacson, C, Langman, G, Shackleford, H, Djearaman, M, Kadiri, S, Alzetani, A, Richards, J, Scarlett, L, Ingram, P, Chee, S, Austin, S, Bajaj, A, Nakas, A, Sodha-Ramdeen, A, Fennell, D, Ang, K, Tufail, M, Chowdhry, M, Scotland, M, Boyles, R, Rathinam, S, Wilson, C, Marrone, D, Dulloo, S, Montero, A, Smith, E, Fontaine, E, Granato, F, Doran, H, Novasio, J, Rammohan, K, Joseph, L, Bishop, P, Shah, R, Moss, S, Joshi, V, Aerts, H, Kaufmann, T, Schwarz, R, Kisistok, J, Sokac, M, Diossy, M, Szallasi, Z, Dijkstra, K, Yuan, Y, Byrne, F, Boos, L, Shum, B, Gerard, C, Schmitt, A, Messiou, C, Cunningham, D, Chau, I, Starling, N, Turner, N, Welsh, L, Jones, R, Droney, J, Banerjee, S, Tatham, K, Jhanji, S, Harrington, K, Okines, A, Reid, A, Young, K, Furness, A, Pickering, L, Nicholson, E, Kumar, S, Wilkinson, K, Swerdlow, A, Wilkinson, R, Hiley, C, Litchfield, K, Mcgranahan, N, Jamal-Hanjani, M, Larkin, J, Turajlic, S, Swanton, C, Downward, J, Kassiotis, G, Ng K. W., Boumelha J., Enfield K. S. S., Almagro J., Cha H., Pich O., Karasaki T., Moore D. A., Salgado R., Sivakumar M., Young G., Molina-Arcas M., de Carne Trecesson S., Anastasiou P., Fendler A., Au L., Shepherd S. T. C., Martinez-Ruiz C., Puttick C., Black J. R. M., Watkins T. B. K., Kim H., Shim S., Faulkner N., Attig J., Veeriah S., Magno N., Ward S., Frankell A. M., Al Bakir M., Lim E. L., Hill M. S., Wilson G. A., Cook D. E., Birkbak N. J., Behrens A., Yousaf N., Popat S., Hackshaw A., Rowan A., Huebner A., Campbell B. B., Bailey C., Lee C., Biswas D., Colliver E., Athanasopoulou F., Zhai H., Rane J. K., Grigoriadis K., Dietzen M., Leung M., Angelova M., Lucas O., Al-Sawaf O., Rosenthal R., Nicod J., Bunkum A., Toncheva A., Abbosh C., Richard C., Naceur-Lombardelli C., Gimeno-Valiente F., Lam J. M., Thol K., Thakkar K., Werner Sunderland M., Forster M. D., Kanu N., Prymas P., Bentham R., Saghafinia S., Quezada S. A., Vanloo S., Zaccaria S., Lee S. M., Hessey S., Liu W. K., Papadatos-Pastos D., Wilson J., Benafif S., Ahmad T., Borg E., Falzon M., Khiroya R., Marafioti T., Sharp A., Pilotti C., Dhanda H. K., Chan K., Gower N., Leslie R., Smith S., Nicholson A. G., Lim E., Herrero J., Castignani C., Larose Cadieux E., Demeulemeester J., Van Loo P., Peggs K. S., Veiga C., Royle G., Collins-Fekete C. -A., Procter A. J., Nair A., Ahmed A., Taylor M. N., Navani N., Thakrar R. M., Lawrence D., Patrini D., Nye E., Stone R. K., Chuter D., MacKenzie M., Fraioli F., Ashford P., Janes S. M., Tanic M., Beck S., Rice A., Devaraj A., Proli C., Kaniu D., Bhayani H., Chavan H., Raubenheimer H., Ambrose L., Malima M., Fernandes N., De Sousa P., Shah P., Booth S., Buderi S. I., Jordan S., Begum S., Boleti E., Stewart A., Magness A., Weeden C. E., Levi D., Gronroos E., Goldman J., Escudero M., Hobson P., Vendramin R., Boeing S., Denner T., Barbe V., Lu W. -T., Hill W., Naito Y., Ramsden Z., Grapa A., Zhang H., AbdulJabbar K., Pan X., Gilbert K., Karamani A., Chain B., Pearce D. R., Karagianni D., Hoxha E., Galvez-Cancino F., Stavrou G., Mastrokalos G., Lowe H. L., Matos I., Reading J. L., Hartley J. A., Selvaraju K., Chen K., Ensell L., Shah M., Vasquez M., Litovchenko M., Chervova O., Pawlik P., Hynds R. E., Lopez S., Gamble S., Ung S. K. A., Bola S. K., Mourikis T. P., Spanswick V., Wu Y., Martinoni Hoogenboom E., Monk F., Holding J. W., Choudhary J., Bhakhri K., Scarci M., Hayward M., Panagiotopoulos N., Gorman P., Stephens R. C. M., Bandula S., Wong Y. N. S., Clark T., Cheyne H., Khalil M., Richardson S., Cruickshank T., Naidu B., Matharu G., Shaw J. A., Riley J., Primrose L., Le Quesne J., Blyth K. G., Kerr A., Clipson A., Chaturvedi A., Dive C., Rothwell D. G., Kilgour E., Tugwood J., Priest L., Oliveira P., Crosbie P., Price G., Cave J., Kerr K. M., Lindsay C. R., Blackhall F. H., Krebs M. G., Summers Y., Kirk A., Thomas M., Asif M., Kostoulas N., Bilancia R., Middleton G., Shackcloth M. J., Leek A., Hodgkinson J. D., Totten N., Dick C., Robinson L., Russell P., Hewish M., Danson S., Lester J. F., Gomes F., Brown K., Carter M., Patel A. J., Osman A., Lacson C., Langman G., Shackleford H., Djearaman M., Kadiri S., Alzetani A., Richards J., Scarlett L., Ingram P., Chee S., Austin S., Bajaj A., Nakas A., Sodha-Ramdeen A., Fennell D. A., Ang K., Tufail M., Chowdhry M. F., Scotland M., Boyles R., Rathinam S., Wilson C., Marrone D., Dulloo S., Montero A., Smith E., Fontaine E., Granato F., Doran H., Novasio J., Rammohan K., Joseph L., Bishop P., Shah R., Moss S., Joshi V., Aerts H. J. W. L., Kaufmann T. L., Schwarz R. F., Kisistok J., Sokac M., Diossy M., Szallasi Z., Dijkstra K., Yuan Y., Byrne F., Boos L. A., Shum B., Gerard C. L., Schmitt A. M., Messiou C., Cunningham D., Chau I., Starling N., Turner N., Welsh L., Jones R. L., Droney J., Banerjee S., Tatham K. C., Jhanji S., Harrington K., Okines A., Reid A., Young K., Furness A. J. S., Pickering L., Nicholson E., Kumar S., Wilkinson K. A., Swerdlow A., Wilkinson R. J., Hiley C. T., Litchfield K., McGranahan N., Jamal-Hanjani M., Larkin J., Lee S. -H., Turajlic S., Swanton C., Downward J., Kassiotis G., Ng, K, Boumelha, J, Enfield, K, Almagro, J, Cha, H, Pich, O, Karasaki, T, Moore, D, Salgado, R, Sivakumar, M, Young, G, Molina-Arcas, M, de Carne Trecesson, S, Anastasiou, P, Fendler, A, Au, L, Shepherd, S, Martinez-Ruiz, C, Puttick, C, Black, J, Watkins, T, Kim, H, Shim, S, Faulkner, N, Attig, J, Veeriah, S, Magno, N, Ward, S, Frankell, A, Al Bakir, M, Lim, E, Hill, M, Wilson, G, Cook, D, Birkbak, N, Behrens, A, Yousaf, N, Popat, S, Hackshaw, A, Rowan, A, Huebner, A, Campbell, B, Bailey, C, Lee, C, Biswas, D, Colliver, E, Athanasopoulou, F, Zhai, H, Rane, J, Grigoriadis, K, Dietzen, M, Leung, M, Angelova, M, Lucas, O, Al-Sawaf, O, Rosenthal, R, Nicod, J, Bunkum, A, Toncheva, A, Abbosh, C, Richard, C, Naceur-Lombardelli, C, Gimeno-Valiente, F, Lam, J, Thol, K, Thakkar, K, Werner Sunderland, M, Forster, M, Kanu, N, Prymas, P, Bentham, R, Saghafinia, S, Quezada, S, Vanloo, S, Zaccaria, S, Lee, S, Hessey, S, Liu, W, Papadatos-Pastos, D, Wilson, J, Benafif, S, Ahmad, T, Borg, E, Falzon, M, Khiroya, R, Marafioti, T, Sharp, A, Pilotti, C, Dhanda, H, Chan, K, Gower, N, Leslie, R, Smith, S, Nicholson, A, Herrero, J, Castignani, C, Larose Cadieux, E, Demeulemeester, J, Van Loo, P, Peggs, K, Veiga, C, Royle, G, Collins-Fekete, C, Procter, A, Nair, A, Ahmed, A, Taylor, M, Navani, N, Thakrar, R, Lawrence, D, Patrini, D, Nye, E, Stone, R, Chuter, D, Mackenzie, M, Fraioli, F, Ashford, P, Janes, S, Tanic, M, Beck, S, Rice, A, Devaraj, A, Proli, C, Kaniu, D, Bhayani, H, Chavan, H, Raubenheimer, H, Ambrose, L, Malima, M, Fernandes, N, De Sousa, P, Shah, P, Booth, S, Buderi, S, Jordan, S, Begum, S, Boleti, E, Stewart, A, Magness, A, Weeden, C, Levi, D, Gronroos, E, Goldman, J, Escudero, M, Hobson, P, Vendramin, R, Boeing, S, Denner, T, Barbe, V, Lu, W, Hill, W, Naito, Y, Ramsden, Z, Grapa, A, Zhang, H, Abduljabbar, K, Pan, X, Gilbert, K, Karamani, A, Chain, B, Pearce, D, Karagianni, D, Hoxha, E, Galvez-Cancino, F, Stavrou, G, Mastrokalos, G, Lowe, H, Matos, I, Reading, J, Hartley, J, Selvaraju, K, Chen, K, Ensell, L, Shah, M, Vasquez, M, Litovchenko, M, Chervova, O, Pawlik, P, Hynds, R, Lopez, S, Gamble, S, Ung, S, Bola, S, Mourikis, T, Spanswick, V, Wu, Y, Martinoni Hoogenboom, E, Monk, F, Holding, J, Choudhary, J, Bhakhri, K, Scarci, M, Hayward, M, Panagiotopoulos, N, Gorman, P, Stephens, R, Bandula, S, Wong, Y, Clark, T, Cheyne, H, Khalil, M, Richardson, S, Cruickshank, T, Naidu, B, Matharu, G, Shaw, J, Riley, J, Primrose, L, Le Quesne, J, Blyth, K, Kerr, A, Clipson, A, Chaturvedi, A, Dive, C, Rothwell, D, Kilgour, E, Tugwood, J, Priest, L, Oliveira, P, Crosbie, P, Price, G, Cave, J, Kerr, K, Lindsay, C, Blackhall, F, Krebs, M, Summers, Y, Kirk, A, Thomas, M, Asif, M, Kostoulas, N, Bilancia, R, Middleton, G, Shackcloth, M, Leek, A, Hodgkinson, J, Totten, N, Dick, C, Robinson, L, Russell, P, Hewish, M, Danson, S, Lester, J, Gomes, F, Brown, K, Carter, M, Patel, A, Osman, A, Lacson, C, Langman, G, Shackleford, H, Djearaman, M, Kadiri, S, Alzetani, A, Richards, J, Scarlett, L, Ingram, P, Chee, S, Austin, S, Bajaj, A, Nakas, A, Sodha-Ramdeen, A, Fennell, D, Ang, K, Tufail, M, Chowdhry, M, Scotland, M, Boyles, R, Rathinam, S, Wilson, C, Marrone, D, Dulloo, S, Montero, A, Smith, E, Fontaine, E, Granato, F, Doran, H, Novasio, J, Rammohan, K, Joseph, L, Bishop, P, Shah, R, Moss, S, Joshi, V, Aerts, H, Kaufmann, T, Schwarz, R, Kisistok, J, Sokac, M, Diossy, M, Szallasi, Z, Dijkstra, K, Yuan, Y, Byrne, F, Boos, L, Shum, B, Gerard, C, Schmitt, A, Messiou, C, Cunningham, D, Chau, I, Starling, N, Turner, N, Welsh, L, Jones, R, Droney, J, Banerjee, S, Tatham, K, Jhanji, S, Harrington, K, Okines, A, Reid, A, Young, K, Furness, A, Pickering, L, Nicholson, E, Kumar, S, Wilkinson, K, Swerdlow, A, Wilkinson, R, Hiley, C, Litchfield, K, Mcgranahan, N, Jamal-Hanjani, M, Larkin, J, Turajlic, S, Swanton, C, Downward, J, Kassiotis, G, Ng K. W., Boumelha J., Enfield K. S. S., Almagro J., Cha H., Pich O., Karasaki T., Moore D. A., Salgado R., Sivakumar M., Young G., Molina-Arcas M., de Carne Trecesson S., Anastasiou P., Fendler A., Au L., Shepherd S. T. C., Martinez-Ruiz C., Puttick C., Black J. R. M., Watkins T. B. K., Kim H., Shim S., Faulkner N., Attig J., Veeriah S., Magno N., Ward S., Frankell A. M., Al Bakir M., Lim E. L., Hill M. S., Wilson G. A., Cook D. E., Birkbak N. J., Behrens A., Yousaf N., Popat S., Hackshaw A., Rowan A., Huebner A., Campbell B. B., Bailey C., Lee C., Biswas D., Colliver E., Athanasopoulou F., Zhai H., Rane J. K., Grigoriadis K., Dietzen M., Leung M., Angelova M., Lucas O., Al-Sawaf O., Rosenthal R., Nicod J., Bunkum A., Toncheva A., Abbosh C., Richard C., Naceur-Lombardelli C., Gimeno-Valiente F., Lam J. M., Thol K., Thakkar K., Werner Sunderland M., Forster M. D., Kanu N., Prymas P., Bentham R., Saghafinia S., Quezada S. A., Vanloo S., Zaccaria S., Lee S. M., Hessey S., Liu W. K., Papadatos-Pastos D., Wilson J., Benafif S., Ahmad T., Borg E., Falzon M., Khiroya R., Marafioti T., Sharp A., Pilotti C., Dhanda H. K., Chan K., Gower N., Leslie R., Smith S., Nicholson A. G., Lim E., Herrero J., Castignani C., Larose Cadieux E., Demeulemeester J., Van Loo P., Peggs K. S., Veiga C., Royle G., Collins-Fekete C. -A., Procter A. J., Nair A., Ahmed A., Taylor M. N., Navani N., Thakrar R. M., Lawrence D., Patrini D., Nye E., Stone R. K., Chuter D., MacKenzie M., Fraioli F., Ashford P., Janes S. M., Tanic M., Beck S., Rice A., Devaraj A., Proli C., Kaniu D., Bhayani H., Chavan H., Raubenheimer H., Ambrose L., Malima M., Fernandes N., De Sousa P., Shah P., Booth S., Buderi S. I., Jordan S., Begum S., Boleti E., Stewart A., Magness A., Weeden C. E., Levi D., Gronroos E., Goldman J., Escudero M., Hobson P., Vendramin R., Boeing S., Denner T., Barbe V., Lu W. -T., Hill W., Naito Y., Ramsden Z., Grapa A., Zhang H., AbdulJabbar K., Pan X., Gilbert K., Karamani A., Chain B., Pearce D. R., Karagianni D., Hoxha E., Galvez-Cancino F., Stavrou G., Mastrokalos G., Lowe H. L., Matos I., Reading J. L., Hartley J. A., Selvaraju K., Chen K., Ensell L., Shah M., Vasquez M., Litovchenko M., Chervova O., Pawlik P., Hynds R. E., Lopez S., Gamble S., Ung S. K. A., Bola S. K., Mourikis T. P., Spanswick V., Wu Y., Martinoni Hoogenboom E., Monk F., Holding J. W., Choudhary J., Bhakhri K., Scarci M., Hayward M., Panagiotopoulos N., Gorman P., Stephens R. C. M., Bandula S., Wong Y. N. S., Clark T., Cheyne H., Khalil M., Richardson S., Cruickshank T., Naidu B., Matharu G., Shaw J. A., Riley J., Primrose L., Le Quesne J., Blyth K. G., Kerr A., Clipson A., Chaturvedi A., Dive C., Rothwell D. G., Kilgour E., Tugwood J., Priest L., Oliveira P., Crosbie P., Price G., Cave J., Kerr K. M., Lindsay C. R., Blackhall F. H., Krebs M. G., Summers Y., Kirk A., Thomas M., Asif M., Kostoulas N., Bilancia R., Middleton G., Shackcloth M. J., Leek A., Hodgkinson J. D., Totten N., Dick C., Robinson L., Russell P., Hewish M., Danson S., Lester J. F., Gomes F., Brown K., Carter M., Patel A. J., Osman A., Lacson C., Langman G., Shackleford H., Djearaman M., Kadiri S., Alzetani A., Richards J., Scarlett L., Ingram P., Chee S., Austin S., Bajaj A., Nakas A., Sodha-Ramdeen A., Fennell D. A., Ang K., Tufail M., Chowdhry M. F., Scotland M., Boyles R., Rathinam S., Wilson C., Marrone D., Dulloo S., Montero A., Smith E., Fontaine E., Granato F., Doran H., Novasio J., Rammohan K., Joseph L., Bishop P., Shah R., Moss S., Joshi V., Aerts H. J. W. L., Kaufmann T. L., Schwarz R. F., Kisistok J., Sokac M., Diossy M., Szallasi Z., Dijkstra K., Yuan Y., Byrne F., Boos L. A., Shum B., Gerard C. L., Schmitt A. M., Messiou C., Cunningham D., Chau I., Starling N., Turner N., Welsh L., Jones R. L., Droney J., Banerjee S., Tatham K. C., Jhanji S., Harrington K., Okines A., Reid A., Young K., Furness A. J. S., Pickering L., Nicholson E., Kumar S., Wilkinson K. A., Swerdlow A., Wilkinson R. J., Hiley C. T., Litchfield K., McGranahan N., Jamal-Hanjani M., Larkin J., Lee S. -H., Turajlic S., Swanton C., Downward J., and Kassiotis G.
Abstract: B cells are frequently found in the margins of solid tumours as organized follicles in ectopic lymphoid organs called tertiary lymphoid structures (TLS)1,2. Although TLS have been found to correlate with improved patient survival and response to immune checkpoint blockade (ICB), the underlying mechanisms of this association remain elusive1,2. Here we investigate lung-resident B cell responses in patients from the TRACERx 421 (Tracking Non-Small-Cell Lung Cancer Evolution Through Therapy) and other lung cancer cohorts, and in a recently established immunogenic mouse model for lung adenocarcinoma3. We find that both human and mouse lung adenocarcinomas elicit local germinal centre responses and tumour-binding antibodies, and further identify endogenous retrovirus (ERV) envelope glycoproteins as a dominant anti-tumour antibody target. ERV-targeting B cell responses are amplified by ICB in both humans and mice, and by targeted inhibition of KRAS(G12C) in the mouse model. ERV-reactive antibodies exert anti-tumour activity that extends survival in the mouse model, and ERV expression predicts the outcome of ICB in human lung adenocarcinoma. Finally, we find that effective immunotherapy in the mouse model requires CXCL13-dependent TLS formation. Conversely, therapeutic CXCL13 treatment potentiates anti-tumour immunity and synergizes with ICB. Our findings provide a possible mechanistic basis for the association of TLS with immunotherapy response.
Published: 2023

30. Quantifying the impact of immunotherapy on RNA dynamics in cancer

Author: Usaite, I, Biswas, D, Dijkstra, K, Watkins, T, Pich, O, Puttick, C, Angelova, M, Thakkar, K, Hiley, C, Birkbak, N, Kok, M, Zaccaria, S, Wu, Y, Litchfield, K, Swanton, C, Kanu, N, Usaite I., Biswas D., Dijkstra K., Watkins T. B. K., Pich O., Puttick C., Angelova M., Thakkar K., Hiley C., Birkbak N., Kok M., Zaccaria S., Wu Y., Litchfield K., Swanton C., Kanu N., Usaite, I, Biswas, D, Dijkstra, K, Watkins, T, Pich, O, Puttick, C, Angelova, M, Thakkar, K, Hiley, C, Birkbak, N, Kok, M, Zaccaria, S, Wu, Y, Litchfield, K, Swanton, C, Kanu, N, Usaite I., Biswas D., Dijkstra K., Watkins T. B. K., Pich O., Puttick C., Angelova M., Thakkar K., Hiley C., Birkbak N., Kok M., Zaccaria S., Wu Y., Litchfield K., Swanton C., and Kanu N.
Abstract: Background Checkpoint inhibitor (CPI) immunotherapies have provided durable clinical responses across a range of solid tumor types for some patients with cancer. Nonetheless, response rates to CPI vary greatly between cancer types. Resolving intratumor transcriptomic changes induced by CPI may improve our understanding of the mechanisms of sensitivity and resistance. Methods We assembled a cohort of longitudinal pre-therapy and on-therapy samples from 174 patients treated with CPI across six cancer types by leveraging transcriptomic sequencing data from five studies. Results Meta-analyses of published RNA markers revealed an on-therapy pattern of immune reinvigoration in patients with breast cancer, which was not discernible pre-therapy, providing biological insight into the impact of CPI on the breast cancer immune microenvironment. We identified 98 breast cancer-specific correlates of CPI response, including 13 genes which are known IO targets, such as toll-like receptors TLR1, TLR4, and TLR8, that could hold potential as combination targets for patients with breast cancer receiving CPI treatment. Furthermore, we demonstrate that a subset of response genes identified in breast cancer are already highly expressed pre-therapy in melanoma, and additionally we establish divergent RNA dynamics between breast cancer and melanoma following CPI treatment, which may suggest distinct immune microenvironments between the two cancer types. Conclusions Overall, delineating longitudinal RNA dynamics following CPI therapy sheds light on the mechanisms underlying diverging response trajectories, and identifies putative targets for combination therapy.
Published: 2023

31. The evolution of lung cancer and impact of subclonal selection in TRACERx

Author: Frankell, A, Dietzen, M, Al Bakir, M, Lim, E, Karasaki, T, Ward, S, Veeriah, S, Colliver, E, Huebner, A, Bunkum, A, Hill, M, Grigoriadis, K, Moore, D, Black, J, Liu, W, Thol, K, Pich, O, Watkins, T, Naceur-Lombardelli, C, Cook, D, Salgado, R, Wilson, G, Bailey, C, Angelova, M, Bentham, R, Martinez-Ruiz, C, Abbosh, C, Nicholson, A, Le Quesne, J, Biswas, D, Rosenthal, R, Puttick, C, Hessey, S, Lee, C, Prymas, P, Toncheva, A, Smith, J, Xing, W, Nicod, J, Price, G, Kerr, K, Naidu, B, Middleton, G, Blyth, K, Fennell, D, Forster, M, Lee, S, Falzon, M, Hewish, M, Shackcloth, M, Benafif, S, Russell, P, Boleti, E, Krebs, M, Lester, J, Papadatos-Pastos, D, Ahmad, T, Thakrar, R, Lawrence, D, Navani, N, Janes, S, Dive, C, Blackhall, F, Summers, Y, Cave, J, Marafioti, T, Herrero, J, Quezada, S, Peggs, K, Schwarz, R, Van Loo, P, Miedema, D, Birkbak, N, Hiley, C, Hackshaw, A, Zaccaria, S, Bajaj, A, Nakas, A, Sodha-Ramdeen, A, Ang, K, Tufail, M, Chowdhry, M, Scotland, M, Boyles, R, Rathinam, S, Wilson, C, Marrone, D, Dulloo, S, Matharu, G, Shaw, J, Riley, J, Primrose, L, Cheyne, H, Khalil, M, Richardson, S, Cruickshank, T, Gilbert, K, Patel, A, Osman, A, Lacson, C, Langman, G, Shackleford, H, Djearaman, M, Kadiri, S, Leek, A, Hodgkinson, J, Totten, N, Montero, A, Smith, E, Fontaine, E, Granato, F, Doran, H, Novasio, J, Rammohan, K, Joseph, L, Bishop, P, Shah, R, Moss, S, Joshi, V, Crosbie, P, Gomes, F, Brown, K, Carter, M, Chaturvedi, A, Priest, L, Oliveira, P, Lindsay, C, Clipson, A, Tugwood, J, Kerr, A, Rothwell, D, Kilgour, E, Aerts, H, Kaufmann, T, Szallasi, Z, Kisistok, J, Sokac, M, Diossy, M, Demeulemeester, J, Stewart, A, Magness, A, Rowan, A, Karamani, A, Chain, B, Campbell, B, Castignani, C, Weeden, C, Richard, C, Pearce, D, Karagianni, D, Levi, D, Hoxha, E, Larose Cadieux, E, Nye, E, Gronroos, E, Galvez-Cancino, F, Athanasopoulou, F, Gimeno-Valiente, F, Kassiotis, G, Stavrou, G, Mastrokalos, G, Zhai, H, Lowe, H, Matos, I, Goldman, J, Reading, J, Rane, J, Lam, J, Hartley, J, Enfield, K, Selvaraju, K, Litchfield, K, Ng, K, Chen, K, Dijkstra, K, Thakkar, K, Ensell, L, Shah, M, Vasquez, M, Litovchenko, M, Werner Sunderland, M, Leung, M, Escudero, M, Tanic, M, Sivakumar, M, Kanu, N, Chervova, O, Lucas, O, Al-Sawaf, O, Hobson, P, Pawlik, P, Stone, R, Hynds, R, Vendramin, R, Saghafinia, S, Lopez, S, Gamble, S, Ung, S, Vanloo, S, Boeing, S, Beck, S, Bola, S, Denner, T, Mourikis, T, Spanswick, V, Barbe, V, Lu, W, Hill, W, Wu, Y, Naito, Y, Ramsden, Z, Veiga, C, Royle, G, Collins-Fekete, C, Fraioli, F, Ashford, P, Clark, T, Borg, E, Wilson, J, Procter, A, Ahmed, A, Taylor, M, Nair, A, Patrini, D, Martinoni Hoogenboom, E, Monk, F, Holding, J, Choudhary, J, Bhakhri, K, Scarci, M, Hayward, M, Panagiotopoulos, N, Gorman, P, Khiroya, R, Stephens, R, Wong, Y, Bandula, S, Sharp, A, Smith, S, Gower, N, Dhanda, H, Chan, K, Pilotti, C, Leslie, R, Grapa, A, Zhang, H, Abduljabbar, K, Pan, X, Yuan, Y, Chuter, D, Mackenzie, M, Chee, S, Alzetani, A, Scarlett, L, Richards, J, Ingram, P, Austin, S, De Sousa, P, Jordan, S, Rice, A, Raubenheimer, H, Bhayani, H, Ambrose, L, Devaraj, A, Chavan, H, Begum, S, Buderi, S, Kaniu, D, Malima, M, Booth, S, Fernandes, N, Shah, P, Proli, C, Danson, S, Robinson, L, Dick, C, Kirk, A, Asif, M, Bilancia, R, Kostoulas, N, Thomas, M, Jamal-Hanjani, M, Mcgranahan, N, Swanton, C, Frankell A. M., Dietzen M., Al Bakir M., Lim E. L., Karasaki T., Ward S., Veeriah S., Colliver E., Huebner A., Bunkum A., Hill M. S., Grigoriadis K., Moore D. A., Black J. R. M., Liu W. K., Thol K., Pich O., Watkins T. B. K., Naceur-Lombardelli C., Cook D. E., Salgado R., Wilson G. A., Bailey C., Angelova M., Bentham R., Martinez-Ruiz C., Abbosh C., Nicholson A. G., Le Quesne J., Biswas D., Rosenthal R., Puttick C., Hessey S., Lee C., Prymas P., Toncheva A., Smith J., Xing W., Nicod J., Price G., Kerr K. M., Naidu B., Middleton G., Blyth K. G., Fennell D. A., Forster M. D., Lee S. M., Falzon M., Hewish M., Shackcloth M. J., Lim E., Benafif S., Russell P., Boleti E., Krebs M. G., Lester J. F., Papadatos-Pastos D., Ahmad T., Thakrar R. M., Lawrence D., Navani N., Janes S. M., Dive C., Blackhall F. H., Summers Y., Cave J., Marafioti T., Herrero J., Quezada S. A., Peggs K. S., Schwarz R. F., Van Loo P., Miedema D. M., Birkbak N. J., Hiley C. T., Hackshaw A., Zaccaria S., Bajaj A., Nakas A., Sodha-Ramdeen A., Ang K., Tufail M., Chowdhry M. F., Scotland M., Boyles R., Rathinam S., Wilson C., Marrone D., Dulloo S., Matharu G., Shaw J. A., Riley J., Primrose L., Cheyne H., Khalil M., Richardson S., Cruickshank T., Gilbert K., Patel A. J., Osman A., Lacson C., Langman G., Shackleford H., Djearaman M., Kadiri S., Leek A., Hodgkinson J. D., Totten N., Montero A., Smith E., Fontaine E., Granato F., Doran H., Novasio J., Rammohan K., Joseph L., Bishop P., Shah R., Moss S., Joshi V., Crosbie P., Gomes F., Brown K., Carter M., Chaturvedi A., Priest L., Oliveira P., Lindsay C. R., Clipson A., Tugwood J., Kerr A., Rothwell D. G., Kilgour E., Aerts H. J. W. L., Kaufmann T. L., Szallasi Z., Kisistok J., Sokac M., Diossy M., Demeulemeester J., Stewart A., Magness A., Rowan A., Karamani A., Chain B., Campbell B. B., Castignani C., Weeden C. E., Richard C., Pearce D. R., Karagianni D., Levi D., Hoxha E., Larose Cadieux E., Nye E., Gronroos E., Galvez-Cancino F., Athanasopoulou F., Gimeno-Valiente F., Kassiotis G., Stavrou G., Mastrokalos G., Zhai H., Lowe H. L., Matos I., Goldman J., Reading J. L., Rane J. K., Lam J. M., Hartley J. A., Enfield K. S. S., Selvaraju K., Litchfield K., Ng K. W., Chen K., Dijkstra K., Thakkar K., Ensell L., Shah M., Vasquez M., Litovchenko M., Werner Sunderland M., Leung M., Escudero M., Tanic M., Sivakumar M., Kanu N., Chervova O., Lucas O., Al-Sawaf O., Hobson P., Pawlik P., Stone R. K., Hynds R. E., Vendramin R., Saghafinia S., Lopez S., Gamble S., Ung S. K. A., Vanloo S., Boeing S., Beck S., Bola S. K., Denner T., Mourikis T. P., Spanswick V., Barbe V., Lu W. -T., Hill W., Wu Y., Naito Y., Ramsden Z., Veiga C., Royle G., Collins-Fekete C. -A., Fraioli F., Ashford P., Clark T., Borg E., Wilson J., Procter A. J., Ahmed A., Taylor M. N., Nair A., Patrini D., Martinoni Hoogenboom E., Monk F., Holding J. W., Choudhary J., Bhakhri K., Scarci M., Hayward M., Panagiotopoulos N., Gorman P., Khiroya R., Stephens R. C., Wong Y. N. S., Bandula S., Sharp A., Smith S., Gower N., Dhanda H. K., Chan K., Pilotti C., Leslie R., Grapa A., Zhang H., AbdulJabbar K., Pan X., Yuan Y., Chuter D., MacKenzie M., Chee S., Alzetani A., Scarlett L., Richards J., Ingram P., Austin S., De Sousa P., Jordan S., Rice A., Raubenheimer H., Bhayani H., Ambrose L., Devaraj A., Chavan H., Begum S., Buderi S. I., Kaniu D., Malima M., Booth S., Fernandes N., Shah P., Proli C., Danson S., Robinson L., Dick C., Kirk A., Asif M., Bilancia R., Kostoulas N., Thomas M., Jamal-Hanjani M., McGranahan N., Swanton C., Frankell, A, Dietzen, M, Al Bakir, M, Lim, E, Karasaki, T, Ward, S, Veeriah, S, Colliver, E, Huebner, A, Bunkum, A, Hill, M, Grigoriadis, K, Moore, D, Black, J, Liu, W, Thol, K, Pich, O, Watkins, T, Naceur-Lombardelli, C, Cook, D, Salgado, R, Wilson, G, Bailey, C, Angelova, M, Bentham, R, Martinez-Ruiz, C, Abbosh, C, Nicholson, A, Le Quesne, J, Biswas, D, Rosenthal, R, Puttick, C, Hessey, S, Lee, C, Prymas, P, Toncheva, A, Smith, J, Xing, W, Nicod, J, Price, G, Kerr, K, Naidu, B, Middleton, G, Blyth, K, Fennell, D, Forster, M, Lee, S, Falzon, M, Hewish, M, Shackcloth, M, Benafif, S, Russell, P, Boleti, E, Krebs, M, Lester, J, Papadatos-Pastos, D, Ahmad, T, Thakrar, R, Lawrence, D, Navani, N, Janes, S, Dive, C, Blackhall, F, Summers, Y, Cave, J, Marafioti, T, Herrero, J, Quezada, S, Peggs, K, Schwarz, R, Van Loo, P, Miedema, D, Birkbak, N, Hiley, C, Hackshaw, A, Zaccaria, S, Bajaj, A, Nakas, A, Sodha-Ramdeen, A, Ang, K, Tufail, M, Chowdhry, M, Scotland, M, Boyles, R, Rathinam, S, Wilson, C, Marrone, D, Dulloo, S, Matharu, G, Shaw, J, Riley, J, Primrose, L, Cheyne, H, Khalil, M, Richardson, S, Cruickshank, T, Gilbert, K, Patel, A, Osman, A, Lacson, C, Langman, G, Shackleford, H, Djearaman, M, Kadiri, S, Leek, A, Hodgkinson, J, Totten, N, Montero, A, Smith, E, Fontaine, E, Granato, F, Doran, H, Novasio, J, Rammohan, K, Joseph, L, Bishop, P, Shah, R, Moss, S, Joshi, V, Crosbie, P, Gomes, F, Brown, K, Carter, M, Chaturvedi, A, Priest, L, Oliveira, P, Lindsay, C, Clipson, A, Tugwood, J, Kerr, A, Rothwell, D, Kilgour, E, Aerts, H, Kaufmann, T, Szallasi, Z, Kisistok, J, Sokac, M, Diossy, M, Demeulemeester, J, Stewart, A, Magness, A, Rowan, A, Karamani, A, Chain, B, Campbell, B, Castignani, C, Weeden, C, Richard, C, Pearce, D, Karagianni, D, Levi, D, Hoxha, E, Larose Cadieux, E, Nye, E, Gronroos, E, Galvez-Cancino, F, Athanasopoulou, F, Gimeno-Valiente, F, Kassiotis, G, Stavrou, G, Mastrokalos, G, Zhai, H, Lowe, H, Matos, I, Goldman, J, Reading, J, Rane, J, Lam, J, Hartley, J, Enfield, K, Selvaraju, K, Litchfield, K, Ng, K, Chen, K, Dijkstra, K, Thakkar, K, Ensell, L, Shah, M, Vasquez, M, Litovchenko, M, Werner Sunderland, M, Leung, M, Escudero, M, Tanic, M, Sivakumar, M, Kanu, N, Chervova, O, Lucas, O, Al-Sawaf, O, Hobson, P, Pawlik, P, Stone, R, Hynds, R, Vendramin, R, Saghafinia, S, Lopez, S, Gamble, S, Ung, S, Vanloo, S, Boeing, S, Beck, S, Bola, S, Denner, T, Mourikis, T, Spanswick, V, Barbe, V, Lu, W, Hill, W, Wu, Y, Naito, Y, Ramsden, Z, Veiga, C, Royle, G, Collins-Fekete, C, Fraioli, F, Ashford, P, Clark, T, Borg, E, Wilson, J, Procter, A, Ahmed, A, Taylor, M, Nair, A, Patrini, D, Martinoni Hoogenboom, E, Monk, F, Holding, J, Choudhary, J, Bhakhri, K, Scarci, M, Hayward, M, Panagiotopoulos, N, Gorman, P, Khiroya, R, Stephens, R, Wong, Y, Bandula, S, Sharp, A, Smith, S, Gower, N, Dhanda, H, Chan, K, Pilotti, C, Leslie, R, Grapa, A, Zhang, H, Abduljabbar, K, Pan, X, Yuan, Y, Chuter, D, Mackenzie, M, Chee, S, Alzetani, A, Scarlett, L, Richards, J, Ingram, P, Austin, S, De Sousa, P, Jordan, S, Rice, A, Raubenheimer, H, Bhayani, H, Ambrose, L, Devaraj, A, Chavan, H, Begum, S, Buderi, S, Kaniu, D, Malima, M, Booth, S, Fernandes, N, Shah, P, Proli, C, Danson, S, Robinson, L, Dick, C, Kirk, A, Asif, M, Bilancia, R, Kostoulas, N, Thomas, M, Jamal-Hanjani, M, Mcgranahan, N, Swanton, C, Frankell A. M., Dietzen M., Al Bakir M., Lim E. L., Karasaki T., Ward S., Veeriah S., Colliver E., Huebner A., Bunkum A., Hill M. S., Grigoriadis K., Moore D. A., Black J. R. M., Liu W. K., Thol K., Pich O., Watkins T. B. K., Naceur-Lombardelli C., Cook D. E., Salgado R., Wilson G. A., Bailey C., Angelova M., Bentham R., Martinez-Ruiz C., Abbosh C., Nicholson A. G., Le Quesne J., Biswas D., Rosenthal R., Puttick C., Hessey S., Lee C., Prymas P., Toncheva A., Smith J., Xing W., Nicod J., Price G., Kerr K. M., Naidu B., Middleton G., Blyth K. G., Fennell D. A., Forster M. D., Lee S. M., Falzon M., Hewish M., Shackcloth M. J., Lim E., Benafif S., Russell P., Boleti E., Krebs M. G., Lester J. F., Papadatos-Pastos D., Ahmad T., Thakrar R. M., Lawrence D., Navani N., Janes S. M., Dive C., Blackhall F. H., Summers Y., Cave J., Marafioti T., Herrero J., Quezada S. A., Peggs K. S., Schwarz R. F., Van Loo P., Miedema D. M., Birkbak N. J., Hiley C. T., Hackshaw A., Zaccaria S., Bajaj A., Nakas A., Sodha-Ramdeen A., Ang K., Tufail M., Chowdhry M. F., Scotland M., Boyles R., Rathinam S., Wilson C., Marrone D., Dulloo S., Matharu G., Shaw J. A., Riley J., Primrose L., Cheyne H., Khalil M., Richardson S., Cruickshank T., Gilbert K., Patel A. J., Osman A., Lacson C., Langman G., Shackleford H., Djearaman M., Kadiri S., Leek A., Hodgkinson J. D., Totten N., Montero A., Smith E., Fontaine E., Granato F., Doran H., Novasio J., Rammohan K., Joseph L., Bishop P., Shah R., Moss S., Joshi V., Crosbie P., Gomes F., Brown K., Carter M., Chaturvedi A., Priest L., Oliveira P., Lindsay C. R., Clipson A., Tugwood J., Kerr A., Rothwell D. G., Kilgour E., Aerts H. J. W. L., Kaufmann T. L., Szallasi Z., Kisistok J., Sokac M., Diossy M., Demeulemeester J., Stewart A., Magness A., Rowan A., Karamani A., Chain B., Campbell B. B., Castignani C., Weeden C. E., Richard C., Pearce D. R., Karagianni D., Levi D., Hoxha E., Larose Cadieux E., Nye E., Gronroos E., Galvez-Cancino F., Athanasopoulou F., Gimeno-Valiente F., Kassiotis G., Stavrou G., Mastrokalos G., Zhai H., Lowe H. L., Matos I., Goldman J., Reading J. L., Rane J. K., Lam J. M., Hartley J. A., Enfield K. S. S., Selvaraju K., Litchfield K., Ng K. W., Chen K., Dijkstra K., Thakkar K., Ensell L., Shah M., Vasquez M., Litovchenko M., Werner Sunderland M., Leung M., Escudero M., Tanic M., Sivakumar M., Kanu N., Chervova O., Lucas O., Al-Sawaf O., Hobson P., Pawlik P., Stone R. K., Hynds R. E., Vendramin R., Saghafinia S., Lopez S., Gamble S., Ung S. K. A., Vanloo S., Boeing S., Beck S., Bola S. K., Denner T., Mourikis T. P., Spanswick V., Barbe V., Lu W. -T., Hill W., Wu Y., Naito Y., Ramsden Z., Veiga C., Royle G., Collins-Fekete C. -A., Fraioli F., Ashford P., Clark T., Borg E., Wilson J., Procter A. J., Ahmed A., Taylor M. N., Nair A., Patrini D., Martinoni Hoogenboom E., Monk F., Holding J. W., Choudhary J., Bhakhri K., Scarci M., Hayward M., Panagiotopoulos N., Gorman P., Khiroya R., Stephens R. C., Wong Y. N. S., Bandula S., Sharp A., Smith S., Gower N., Dhanda H. K., Chan K., Pilotti C., Leslie R., Grapa A., Zhang H., AbdulJabbar K., Pan X., Yuan Y., Chuter D., MacKenzie M., Chee S., Alzetani A., Scarlett L., Richards J., Ingram P., Austin S., De Sousa P., Jordan S., Rice A., Raubenheimer H., Bhayani H., Ambrose L., Devaraj A., Chavan H., Begum S., Buderi S. I., Kaniu D., Malima M., Booth S., Fernandes N., Shah P., Proli C., Danson S., Robinson L., Dick C., Kirk A., Asif M., Bilancia R., Kostoulas N., Thomas M., Jamal-Hanjani M., McGranahan N., and Swanton C.
Abstract: Lung cancer is the leading cause of cancer-associated mortality worldwide1. Here we analysed 1,644 tumour regions sampled at surgery or during follow-up from the first 421 patients with non-small cell lung cancer prospectively enrolled into the TRACERx study. This project aims to decipher lung cancer evolution and address the primary study endpoint: determining the relationship between intratumour heterogeneity and clinical outcome. In lung adenocarcinoma, mutations in 22 out of 40 common cancer genes were under significant subclonal selection, including classical tumour initiators such as TP53 and KRAS. We defined evolutionary dependencies between drivers, mutational processes and whole genome doubling (WGD) events. Despite patients having a history of smoking, 8% of lung adenocarcinomas lacked evidence of tobacco-induced mutagenesis. These tumours also had similar detection rates for EGFR mutations and for RET, ROS1, ALK and MET oncogenic isoforms compared with tumours in never-smokers, which suggests that they have a similar aetiology and pathogenesis. Large subclonal expansions were associated with positive subclonal selection. Patients with tumours harbouring recent subclonal expansions, on the terminus of a phylogenetic branch, had significantly shorter disease-free survival. Subclonal WGD was detected in 19% of tumours, and 10% of tumours harboured multiple subclonal WGDs in parallel. Subclonal, but not truncal, WGD was associated with shorter disease-free survival. Copy number heterogeneity was associated with extrathoracic relapse within 1 year after surgery. These data demonstrate the importance of clonal expansion, WGD and copy number instability in determining the timing and patterns of relapse in non-small cell lung cancer and provide a comprehensive clinical cancer evolutionary data resource.
Published: 2023

32. Telomerase : a prognostic marker and therapeutic target

Author: Thakkar, Dipti S.
Subjects: 363.25, Q Science (General), R Medicine (General), QM Human anatomy
Abstract: Malignant glioma is the most common and aggressive form of tumours and is usually refractory to therapy. Telomerase and its altered activity, distinguishing cancer cells, is an attractive molecular target in glioma therapeutics. The aim of this thesis was to silence telomerase at the genetic level with a view to highlight the changes caused in the cancer proteome and identify the potential downstream pathways controlled by telomerase in tumour progression and maintenance. A comprehensive proteomic study utilizing 2D-DIGE and MALDI-TOF were used to assess the effect of inhibiting two different regulatory mechanisms of telomerase in glioma. RNAi was used to target hTERT and Hsp90α. Inhibition of telomerase activity resulted in down regulation of various cytoskeletal proteins with correlative evidence of the involvement of telomerase in regulating the expression of vimentin. Vimentin plays an important role in tumour metastasis and is used as an indicator of glioma metastasis. Inhibition of telomerase via sihTERT results in the down regulation of vimentin expression in glioma cell lines in a grade specific manner. While, 9 of 12 glioblastoma tissues (grade IV) showed vimentin to be highly expressed, its expression was absent in lower grades and normal tissues. This suggests that vimentin can be potentially used as a glioma progressive marker. This is the first study to report the potential involvement of telomerase in the regulation of vimentin expression. This study also identified that combination therapy, comprising siRNA targeted towards telomerase regulatory mechanisms and the natural product Epigallocatechin-3-gallate (ECGC), results in decreased cell viability producing comparable results to that of other chemotherapeutic drugs.
Published: 2010

33. Monitoring of rail/wheel interaction using acoustic emission

Author: Thakkar, Nirav Ashokkumar, Reuben, R. L., and Steel, J. A.
Subjects: 629.04
Abstract: The work presented in this thesis is related to the condition monitoring of rail-wheel interaction using Acoustic Emission (AE), the principle being that both normal and abnormal rolling give rise to AE, features of which are related to the mechanical intensity of the interaction and hence the stress range (or stress intensity factor range) to which sections of track is being exposed. Most of the work was carried out on a model wheel running on a model circular track, which was first characterised using a simulated source before studying the wave propagation from a continuously moving (wheel) source. Using a number of sensor arrays placed on the track, primary wave propagation characteristics such as wave speeds and attenuation coefficients and also secondary wave propagation characteristics such as reflection and transmission from and through the joint. A high speed camera was used to confirm, that wheel slip does not occur at the wheel speeds and loads of interest. A simple analytical model was derived using the measured wave propagation characteristics which describes the expected AE recorded at a track-mounted sensor as the wheel approaches and recedes. Using the analytical model, the effect of increasing wheel speed and axle load on the normal rolling signal was measured. Wheel rattling was observed, particularly at lower wheel speeds and loads, and this was eliminated in some trails by introducing a spacer. The effect of minor track defects and wheel flange rubbing on the track was also studied, where the comparison of the expected normal running signal with excursions above background allowed the locations of track defects to be identified. Finally, a set of experiments were carried out with simulated wheel defects. The signals were analysed using the principle of demodulated frequency resonance and matching to the expected pulse train spectra. . The findings of the work, along with a limited set of field tests on actual train-track interactions allows recommendations to be made for the deployment of sensors for cumulative damage monitoring on critical areas of track.
Published: 2009

34. Irony and the rhetoric of revolution in the work of Juan Rulfo

Author: Thakkar, Amit
Subjects: 863.64
Published: 2004
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35. RecQ Helicase Somatic Alterations in Cancer.

Author: Thakkar, Megha, Thakkar, Megha, Lee, Jamie, Meyer, Stefan, Chang, Vivian, Thakkar, Megha, Thakkar, Megha, Lee, Jamie, Meyer, Stefan, and Chang, Vivian
Abstract: Named the caretakers of the genome, RecQ helicases function in several pathways to maintain genomic stability and repair DNA. This highly conserved family of enzymes consist of five different proteins in humans: RECQL1, BLM, WRN, RECQL4, and RECQL5. Biallelic germline mutations in BLM, WRN, and RECQL4 have been linked to rare cancer-predisposing syndromes. Emerging research has also implicated somatic alterations in RecQ helicases in a variety of cancers, including hematological malignancies, breast cancer, osteosarcoma, amongst others. These alterations in RecQ helicases, particularly overexpression, may lead to increased resistance of cancer cells to conventional chemotherapy. Downregulation of these proteins may allow for increased sensitivity to chemotherapy, and, therefore, may be important therapeutic targets. Here we provide a comprehensive review of our current understanding of the role of RecQ DNA helicases in cancer and discuss the potential therapeutic opportunities in targeting these helicases.
Published: 2022

36. Validation of the OAKS prognostic model for acute kidney injury after gastrointestinal surgery

Author: Ahmed, W, Bhatia, S, Mclean, K, Khaw, R, Baker, D, Kamarajah, S, Bell, S, Nepogodiev, D, Harrison, E, Glasbey, J, Borakati, A, Burke, J, Drake, T, Bath, M, Claireaux, H, Gundogan, B, Mohan, M, Deekonda, P, Kong, C, Joyce, H, Mcnamee, L, Woin, E, Khatri, C, Fitzgerald, J, Bhangu, A, Arulkumaran, N, Duthie, F, Hughes, J, Pinkney, T, Prowle, J, Richards, T, Thomas, M, Blanco-Colino, R, Chapman, S, Pata, F, Pellino, G, Sgro, A, van Elst, T, Van Straten, S, Knowles, C, Dynes, K, Patel, M, Patel, P, Wigley, C, Suresh, R, Shaw, A, Klimach, S, Jull, P, Evans, D, Preece, R, Ibrahim, I, Manikavasagar, V, Smith, R, Brown, F, Teo, R, Sim, D, Logan, A, Barai, I, Amin, H, Suresh, S, Sethi, R, Gul, W, Bolton, W, Corbridge, O, Horne, L, Attalla, M, Morley, R, Robinson, C, Hoskins, T, Mcallister, R, Lee, S, Dennis, Y, Nixon, G, Heywood, E, Wilson, H, Ng, L, Samaraweera, S, Mills, A, Doherty, C, Belchos, J, Phan, V, Lim, M, Miller, F, Chouari, T, Gardner, T, Goergen, N, Hayes, J, Macleod, C, Mccormack, R, Mckinley, A, Mckinstry, S, Milligan, W, Ooi, L, Rafiq, N, Sammut, T, Sinclair, E, Smith, M, Wong, J, Ablett, A, Tie-Gill, T, Ramsay, G, De Paola, L, Mcguckin, S, Alshakhs, A, Ahmeidat, A, Francis, A, Baker, C, Boulton, A, Collins, J, Copley, H, Fearnhead, N, Fox, H, Mah, T, Mckenna, J, Naruka, V, Nigam, N, Nourallah, B, Perera, S, Qureshi, A, Saggar, S, Sun, L, Wang, X, Yang, D, Ali, Z, Mullarkey, L, Walshe, R, Lewis, E, Berry, B, Moneim, J, Mookerjee, S, Al-Hadithi, A, Caroll, P, Doyle, C, Elangovan, S, Falamarzi, A, Gascon Perai, K, Greenan, E, Jain, D, Lang-Orsini, M, Lim, S, O'Byrne, L, Ridgway, P, Van der Laan, S, Arthur, J, Barclay, J, Bradley, P, Edwin, C, Finch, E, Hayashi, E, Hopkins, M, Kelly, D, Kelly, M, Mccartan, N, Ormrod, A, Pakenham, A, Christy, S, Hayward, J, Hitchen, C, Kishore, A, Martins, T, Philomen, J, Rao, R, Rickards, C, Burns, N, Copeland, M, Durand, C, Dyal, A, Ghaffar, A, Gidwani, A, Grant, M, Gribbon, C, Gruhn, A, Leer, M, Ojofeitimi, O, Carroll, L, Hylands, A, Delaugere, L, Reveendran, D, Ahmad, K, Beattie, G, Beatty, M, Campbell, G, Donaldson, G, Graham, S, Holmes, D, Kanabar, S, Liu, H, Mccann, C, Stewart, R, Vara, S, Coulter, C, Ralston, C, Laverty, L, Gallagher, P, Ajibola-Taylor, O, Andah, E, Ani, C, Cabdi, N, Ito, G, Jones, M, Komoriyama, A, Titu, L, Ahmed, A, Yeo, Y, Elliott, D, Bennett, J, Mcnamara, M, Sivarajah, S, Dunmore, C, Basra, M, Gallogly, P, Harinath, G, Leong, S, Pradhan, A, Siddiqui, I, Zaat, S, Ali, A, Galea, M, Looi, W, Ng, J, Farhan-Alanie, M, Aitken, G, Nair, M, Aly, M, Buari, M, Atkin, G, Azizi, A, Cargill, Z, China, Z, Elliot, J, Jebakumar, R, Lam, J, Mudalige, G, Onyerindu, C, Renju, M, Shankar Babu, V, Ahmed, K, Sheikh, Z, Monks, M, Lehmann, J, Rotimi, O, Hussain, M, Joji, N, Lovett, B, Mownah, H, Dwyer-Hemmings, L, Busuttil, A, Powell, J, Hensher, C, Vivian, F, Ali, B, Cresswell, B, Dhillon, A, Dupaguntla, Y, Hungwe, C, Lowe-Zinola, J, Tsang, J, Wcislo, K, Bevan, K, Cardus, C, Duggal, A, Hossain, S, Mchugh, M, Scott, M, Millar, Z, Hirosue, S, Ogunmwonyi, I, Nakakande, D, Chan, F, Evans, R, Gurung, E, Haughey, B, Jacob-Ramsdale, B, Kerr, M, Lee, J, Mccann, E, O'Boyle, K, Reid, N, Kwek, I, Gaze, H, Nirmalanantha, A, Bin Amran, M, Foulkes, A, Jones, N, Lau, I, Hayat, F, Hodgson, S, Johnston, R, Jones, W, Khan, M, Linn, T, Long, S, Seetharam, P, Shaman, S, Smart, B, Pillai, S, Khoury, G, Powell, T, Maleyko, I, Sangheli, A, Ransome, M, Isse, M, Aromolaran, O, Bholah, H, Anilkumar, A, Davies, J, Griffith, J, Hughes, B, Islam, Y, Kidanu, D, Mushaini, N, Qamar, I, Robinson, H, Schramm, M, Yan Tan, C, Murray, V, Theocharidou, L, Malik, T, Janmohamed, I, Carhart, B, Khan, A, Apperley, H, Billyard, C, Blazeby, J, Cannon, S, Carse, S, Gopfert, A, Loizidou, A, Parkin, J, Sanders, E, Sharma, S, Slade, G, Telfer, R, Whybrow Huppatz, I, Worley, E, Asif, A, Hullait, R, Quinn, P, Rylance, A, Butt, S, Leathes, J, Chandramoorthy, L, Friend, C, Harris, L, Jain, P, Karim, M, Killington, K, Mcgillicuddy, J, Rafferty, C, Rahunathan, N, Rayne, T, Varathan, Y, Verma, N, Zanichelli, D, Arneill, M, Campbell, B, Crozier, L, Henry, J, Mccusker, C, Prabakaran, P, Wilson, R, Karelia, S, Clements, J, Rainey, M, Asif, U, Connor, M, Dindyal, S, Math, N, Pagarkar, A, Saleem, H, Seth, I, Standfield, N, Swartbol, T, Adamson, R, Choi, J, El Tokhy, O, Ho, W, Javaid, N, Mehdi, A, Menon, D, Plumptre, I, Sturrock, S, Turner, J, Warren, O, Joshi, N, Rahman, A, Gallagher, M, Crane, E, Ferris, B, Gadsby, C, Smallwood, J, Vipond, M, Wilson, V, Amarnath, T, Doshi, A, Gregory, C, Kandiah, K, Powell, B, Spoor, H, Toh, C, Vizor, R, Rebuffa, N, Abdelgalil, R, Siaw Yen Lai, R, Smith, E, Common, M, Dunleavy, K, Harris, S, Luo, C, Mesbah, Z, Prem Kumar, A, Redmond, A, Skulsky, S, Walsh, T, Daly, D, Deery, L, Epanomeritakis, E, Harty, M, Kane, D, Khan, K, Mackey, R, Mcconville, J, Mcginnity, K, Wong, H, Ang, A, Kee, J, Leung, E, Norman, S, Palaniappan, S, Partha Sarathy, P, Yeoh, T, Frost, J, Hazeldine, P, Jones, L, Karbowiak, M, Macdonald, C, Mutarambirwa, A, Omotade, A, Runkel, M, Ryan, G, Sawers, N, Searle, C, Vig, S, Hlukha, L, Pike, G, Kamel, F, Thakkar, R, Mcauliffe, O, Ahmad, A, Mcgartland, R, Sim, R, Song, A, Wayman, J, Brown, R, Chang, L, Concannon, K, Crilly, C, Arnold, T, Burgin, A, Cadden, F, Choy, C, Coleman, M, Lim, D, Luk, J, Mahankali-Rao, P, Prudence-Taylor, A, Ramakrishnan, D, Russell, J, Fawole, A, Gohil, J, Green, B, Hussain, A, Mcmenamin, L, Tang, M, Azmi, F, Benchetrit, S, Cope, T, Haque, A, Harlinska, A, Holdsworth, R, Ivo, T, Martin, J, Nisar, T, Patel, A, Sasapu, K, Trevett, J, Vernet, G, Aamir, A, Bird, C, Durham-Hall, A, Gibson, W, Hartley, J, May, N, Maynard, V, Goble, M, Downs, E, Wheldon, L, Baggus, E, Mandal, A, Nayeem, A, Ahmed, S, Fradley, W, Johnson, S, McDonald Wood, C, O'Brien, M, Orbell, J, Stringfellow, T, Tenters, F, Tresidder, S, Wilson, C, Gallagher, S, Criswell, T, Ward, J, Mukkavilli, A, Stubbs, B, Fordyce, W, Cheung, W, Grant, A, Tod, N, Yi Tew, Z, Suchdev, N, Wei Lim, S, Bews-Hair, M, Lim, Z, Vella-Baldacchino, M, Auckburally, S, Chopada, A, Easdon, S, Goodson, R, Mccurdie, F, Narouz, M, Radford, A, Rea, E, Taylor, O, Yu, T, Sookramanien, S, Chan, A, Bointas, G, Alfa-Wali, M, Amani, L, Auluck, I, Bruce, P, Emberton, J, Kumar, R, Lagzouli, N, Mehta, A, Murtaza, A, Raja, M, Dennahy, I, Frew, K, Given, A, He, Y, Macdonald, E, Mcvinnie, D, Ng, S, Pettit, A, Berthaume-Hawkins, S, Charnley, R, Fenton, K, Jones, D, Murphy, C, Reehal, R, Seraj, S, Shang, E, Tonks, A, White, P, Yeo, A, Paul, M, Ward, K, Bagnall, M, Chong, P, Gabriel, R, Patel, N, Richardson, E, Symons, L, Aubrey-Jones, D, Dawood, S, Dobrzynska, M, Faulkner, S, Griffiths, H, Mahmood, F, Perry, M, Power, A, Simpson, R, Pherwani, S, Wang, K, Mitchell, L, Heyworth, J, Ayyar, S, Brobbey, P, Burrows, A, Elder, P, Ganyani, R, Horseman, C, Hurst, P, Mann, H, Marimuthu, K, Mcbride, S, Pilsworth, E, Powers, N, Stanier, P, Obukofe, R, Polson, R, Mason, D, Mackenzie, E, Innes, R, Kersey, T, Kopczynska, M, Langasco, N, Rajagopal, R, Russell, C, Doyle, N, Habib, Z, Zardab, M, Sartaj, F, Farooq, H, Tabibi, M, Imam, L, Atkins, B, Beasley, W, Cheng Lim, Z, Gill, A, Li Ang, H, Williams, H, Yogeswara, T, Drury, D, James, S, Barnett, R, Teasdale, A, Thomas, D, Williams, R, Najabat-Lattif, H, Akram, B, Carter, R, Fam, M, Fong, J, Latter, J, Long, M, Mackinnon, S, Mckenzie, C, Osmanska, J, Raghuvir, V, Shafi, A, Tsang, K, Walker, L, Cahya, E, Lou, G, Coyle, M, Homyer, K, Zhu, L, Woods, M, Bountra, K, Coldicutt, O, Fletcher, D, Hudson, S, Iqbal, S, Lopez Bernal, T, Moss-Lawton, F, Suchett-Kay, I, Chang, J, O'Callaghan, H, Suchett-Kaye, I, Mihailidis, T, Cardwell, A, Edgerton, K, Laws, J, Rai, A, Robinson, K, Waite, K, Youssef, H, Alawattegama, H, Seite, E, Barrett, A, Riordan, E, Lam, W, Dowdeswell, M, Mulvenna, C, Knight, C, Koo, P, Lazarou, A, Stanger, S, Thorn, C, Triniman, M, Netke, T, Awokoya, O, Gurowich, L, Dhera, K, Hossaini, S, Botha, A, Boyles, L, Cumming, S, Deepak, S, Ezzat, A, Fowler, A, Gwozdz, A, Hussain, S, Khan, S, Li, H, Lu Morrell, B, Neville, J, Nitiahpapand, R, Pickering, O, Sagoo, H, Sharma, E, Welsh, K, Williams, L, Hayat, S, Tincknell, L, Spazzapan, M, Teeling, F, Sysum, K, Denley, S, Latter, M, Agarwal, M, Al-Saadi, N, Bhambra, R, Gupta, A, Jawad, Z, Jiao, L, Mahir, G, Singagireson, S, Thoms, B, Tseu, B, Wei, R, Yang, N, Britton, N, Leinhardt, D, Mahfooz, M, Palkhi, A, Price, M, Sheikh, S, Barker, M, Bowley, D, Cant, M, Datta, U, Farooqi, M, Lee, A, Morley, G, Naushad Amin, M, Parry, A, Patel, S, Strang, S, Yoganayagam, N, Guruswamy, M, Beedham, W, Brazier, E, Elghobashy, M, Bajaj, M, Etel, E, Adlan, A, Chandramoorthy, S, Choudhary, Y, Das, K, Feldman, M, France, B, Grace, R, Puddy, H, Soor, P, Kisiel, A, Woodmass, M, Hayden, H, Ali, Y, Husain, S, Ali, M, Dhillon, P, Faraj, A, Gerard, L, Glover, M, Imran, H, Kim, S, Patrick, Y, Peto, J, Prabhudesai, A, Tang, A, Vadgama, N, Dhaliwal, R, Ecclestone, T, Harris, A, Ong, D, Patel, D, Philp, C, Stewart, E, Wang, L, Wong, E, Xu, Y, Ashaye, T, Fozard, T, Galloway, F, Kaptanis, S, Mistry, P, Nguyen, T, Olagbaiye, F, Osman, M, Philip, Z, Rembacken, R, Tayeh, S, Theodoropoulou, K, Liu, F, Arnold, A, Pedersen, A, Cunha, P, Ahmed, M, Al Zawawi, S, Kudva, V, Herman, A, Lau, J, Saha, A, Trotter, M, Miscampbell, M, Robinson, A, Johnston, J, Dharni, A, Lamb, S, Westerman, T, Adeleye, O, Cave, D, Gunwa, T, Magalhaes, J, Makwana, S, Mason, R, Parish, M, Regan, H, Renwick, P, Roberts, G, Salekin, D, Sivakumar, C, Tariq, A, Liew, I, Mcdade, A, Stewart, D, Evans, E, Campbell, L, Gillespie, M, Cheong, C, Hague, M, Hudson-Peacock, N, Jackson, C, James, F, Pitt, J, Walker, E, Kulathevanayagam, K, Varghese, A, Ike, S, Aftab, R, Ang, J, Anwar, S, Battle, J, Budd, E, Chui, J, Crook, H, Davies, P, Easby, S, Hackney, E, Ho, B, Imam, S, Rammell, J, Chu, T, Baljer, B, Mogg, J, Rai, P, Andrews, H, Perry, C, Schinle, P, Ahmed, P, Aquilina, T, Balai, E, Church, M, Cumber, E, Curtis, A, Davies, G, Dumann, E, Greenhalgh, S, Kim, P, King, S, Metcalfe, K, Passby, L, Redgrave, N, Soonawalla, Z, Waters, S, Zornoza, A, Williams, M, Smillie, R, Goetz, J, Appleby, E, Fadipe, T, Vaughan-Burleigh, S, Davies, R, Gulzar, I, Hole, J, Hull, K, Ishaq, H, Karaj, J, Kelkar, A, Love, E, Thakrar, D, Vine, M, Waterman, A, James, P, Puri, G, Hussain, P, Flather, R, Cutler, A, Pathak, S, Sheldon, J, Collicott, T, al-Ausi, M, Ko, M, Dib, N, Francis, N, Hanson, M, Ingleton, R, Sadanand, K, Sukirthan, N, Mondal, A, Jovaisaite, A, Shah, S, Khalid, N, Gutmann, D, Davison, S, Alame, Y, Syed, L, Owen, W, Arnell, S, Ball, M, Bassam, N, Beghal, G, Chang, A, Dawe, V, George, A, Huq, T, Ikram, B, Kanapeckaite, L, Ramjas, D, Rushd, A, Sait, S, Serry, M, Yardimci, E, Kalderon, R, Ahsan, S, Anthony-Uzoeto, U, Macleod Hall, C, Zheng, S, Wynter, K, Capella, S, Chenciner, L, Episkopos, C, Karam, E, Mccarthy, C, Moore-Kelly, W, Watson, N, Nadama, H, James, C, Sapre, D, Ghosh, R, Baird, J, 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S., Toma T., Wadood Q., Yip J., Charalambides M., Clave Llavall A., Williamson E., Bharwada Y., Zearmal S., Evans H., Panikkar M., de la Cruz G., Caplan J., Ainger E., Busti S., Cunliffe L., Flamini T., Gaffing S., Moorcroft C., Peter M., Simpson L., Stokes E., Stott G., Wilson J., York J., Yousaf A., Ruparelia A., Tanvir T., Soare C., Pang Y. L., Trotter J., Zaidi A., Thakrar V., Brown M., Goaman A., Hodgson B., Ijeomah A., Iroegbu U., Kaur G., Lowe C., Mahmood S., Sattar Z., Sen P., Szuman A., Abbas N., Anto N., Bhome R., Eccles L., Elliott J., Hughes E. J., Jones A., Karunatilleke A. S., Knight J. S., Manson C. C. F., Mekhail I., Michaels L., Noton T. M., Okenyi E., Reeves T., Yasin I. H., Pulickal P., Ahmed H., Parnell J., Lennock S., Ford V., Banfield D. A., Harris R., Mason-Apps C., Roe T., Sandhu J., Shafiq N., Stickler E., Tam J. P., Williams L. 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L., Porter T., Potluri S., Stechman M., Tate S., Thomas D., Walford B., Auld F., Bleakley A., Johnston S., Jones C., Khaw J., Milne S., O'Neill S., Singh K. K. R., Swan A., Thorley N., Yalamarthi S., Yin Z. D., Balian V., Bana R., Clark K., Livesey C., McLachlan G., Mohammad M., Pranesh N., Richards C., Ross F., Sajid M., Liversedge G., Carrington Z., Windebank J., Izzarina A., Akbani U., Craven J., Aldarragi A., Harding S., Millward A., Brooke M., Francombe J., Gresly J., Hutchinson S., Kerrigan K., Matthews E., Nur S., Parsons L., Sandhu A., Vyas M., White F., Zulkifli A., Zuzarte L., Shortland T. C., Bedford M., Al-Mousawi A., Arya J., Azam S., Azri Yahaya A., Gill K., Hallan R., Hathaway C., Leptidis I., McDonagh L., Mitrasinovic S., Mushtaq N., Pang N., Peiris G. B., Rinkoff S., Gopalan V., Midgen A., Khadka P., Cheng O., Taneja S., Manobharath N., Chan L., Christopher E., Gonzalez-Ciscar A., Graham C. J., Lim H., Paterson H. 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E., Sagnotta A., Di Cintio A., Gemini A., Trastulli S., De Luca M., Desiderio J., Gubbiotti F., Campagnaro T., Pedrazzani C., Turri G., Lazzarini E., Conti C., Ruzzenente A., Petrelli F., Marziali I., Mazzocato S., Vergari R., Piazzai F., Kubolli I., Aggiusti A., Paolucci A., Ortenzi M., Gallo G., Clerico G., De Santi G., Bitonti M. F., Trompetto M., Realis Luc A., Papandrea M., Cerra C., Pirillo M., Cravano S., Libri I., Laquatra N., Isabello A., De Luca E., Testa V., Morino M., Mistrangelo M., Sinibaldi G., Angelucci G. P., Scaramuzzo R., Larcinese A., Fioriti C., Picone E., Nardi M., Di Candido F., Spinelli A., Marco M., Bevilacqua M., Maroli A., Colombo F., Cigognini M., Zaffaroni G., Maffioli A., Colombo S., Bondurri A., Sampietro G., Foschi D., Perrone G., Bonati E., Aresu S., Saba A., Biancafarina A., Angelini M., Andolfi E., Miranda E., Scricciolo M., Provenza G., Cavallina G., Frezza B., Fontani A., Malatesti R., Pellicano G. A., Ceccarelli G., Canonico G., Falsetti E., Pagnanelli M., De Nardi P., Rosati R., Marcocci G., Vignali A., Quattromani R., Curletti G., Galleano R., Malerba M., Percivale A., Ghazouani O., Reggiani L., Spirito C., Bini R., de Manzoni Garberini A., Impellizzeri H., Moretto G., Bacchion M., Casaril A., Inama M., Creciun M., Vitali M., Cillara N., Mosino L., Peddis M., Melis S., De Donno G., Aru A. C., Loche G. A., Tutino R., Licari L., Campanella S., Profita G., Falco N., Rotolo G., Venturelli P., De Marco P., Marciano M., Picciariello A., Chetta N., Aquilino F., Papagni V., Coletta D., Cerasari S., Galiffa G., Lapolla P., Del Basso C., Cirillo B., De Toma G., Fazzi K., Bini S., De Padua C., Savino G., Finotti E., Ferrara F., Stella M., Gobatti D., Tamini N., Brenna R., Giani A., Tirotta F., Famularo S., Angrisani M., Ceresoli M., Talamo G., Sucameli F., Gennai A., Moggia E., Bianchi C., Bonfante P., Macina S., Feleppa C., Imperatore M., Berti S., Parini D., Lanari J., Giamundo P., Lo Conte A., Pagano G., Manigrasso M., Danzi M., Amato R., Anastasio L., Mastella F., Basile R., Peltrini R., Marra E., Luglio G., Giglio M., Anoldo P., Vertaldi S., Grimaldi L., Tammaro N., Ripetti V., D'Alessio R., Benvenuto D., Pesce A., Menduni N., Giudicissi R., Zalla T., Baraghini M., Romoli L., Calussi M., Vellei S., Genzano C., Feroci F., Vita M., Giani I., Goldin E., Ciccioli E., Galgano A., Zuin M., Bettella A., Barina A., Vendramin E., Palano G., Schiavone D., Rega D., La Manna V., Migliore G., Aversano A., Fares Bucci A., Belli A., Andriola V., Lafranceschina S., Gordini L., Erdas E., Podda F., Cappellacci F., Salaris C., Sanna S., Marcialis J., Longheu A., Foppa C., Coratti F., Montanelli P., Grandi S., Nelli T., Ben Khaled N., Cammelli F., Ferrini E., Billo M. E., Piccolo G., Romano S., Gaetano P., Pilotta F., Baldassarre L., Birindelli A., D'Errico U., Bianchini S., Ferrari C., Franceschi A., Caristo G., Ballarini Z., Romelli M., Ruggiero S., Percassi A., Milone M., De Rosa M., Pipitone Federico N. S., Molteni B., Magri Piccinini A., Tilocca P. L., Marrosu A. G., Scognamillo F., Pala C., Attene F., Carboni L., Ruggiu M. W., Gabbas G., Sancini G., Roggiani A., Balsamo F., Gori A., Cuicchi D., Vittori L., Piozzi G. N., Tringali D., Bevilacqua E., Panizzo V., Lauretta A., Poillucci G., Mulas S., Simcikas D., Samalavicius N. E., Nutautiene V., Zeromskas P., Jurgaitis J., Aliosin O., Slepavicius A., Eismontas V., Kybransiene M., Portelli L., Cachia C., Cefai C., Youssef Y., Degaetano D., Debono S., Sammut M., Cassar J., Sammut K., Andrejevic P., van Wijnbergen J. W. M., Dinger T. L., ten Doesschate S. F. H., van Dalen A. S. H. M., Looijen R. C., Becker M. A. J., Comert D., Stellingwerf M. E., Abdulrahman N., van den Bos D. D., Gruter A., Vroom Y., Voeten D. M., Feenstra T., de Roy van Zuidewijn D., Hansmann M., Nasimi B., Gerdsen M., Stijns R. C. H., Leow T. Y. S., Penningnieuwland G., Davids J., Medina Feliz J., Kuiper S. Z., Sluijpers N. R. F., van de Pas K. G. H., Pruijssers S. R., Molenaar C. J. L., Thomas G., Farik S., Chen S. Y., Kilpatrick K., Kim D. H., Ong H. I., Elliott B. M., Geneta V. P., Alsadat R., Cherry R., Chapman D. A., Singh N., Clucas A., Gatenby G., Kelly B., Ruppeldt P., McIntosh N. D., Li Y., Wilton S., McLaughlin S. J. P., Kearney J., Sprosen H., Kerckhoffs P., Kandelaki H., Welman D., Coulter J., Morreau M., Li E., Rankin A., Winders J., Skipworth C., Peng S. L., Campbell S., Lim Y. K., Yassaie S. S., Dixon S., Yassaie S., Murray M., Haran C., Koh S., Wilms H., Dalzell F., Tewhaiti-Smith J., Kader T., Yam S. T., Dahya D., Hardie Boys M., Fleischl W., Desmond B., Tan J., Skavysh A., Castro J., Orelhas L., Santos J., Pacheco A., Rocha A. F., Jervis M. J., Pedro V., Paixao V., Guerreiro A., Melo D., Laranjeira A., Machado A., Horta V., Rocha-Melo M., Patricio J., Pereira M., Lima R., Cinza A. M., Oliveira J., Velez C., Senhorinho R., Catarino S., Aveiro D., Couto M., Loureiro A. R., Neves-Marques C., Louro T., Morgado M., Ferreira A. S., Alves M., Oliveira N., Lerias R., Estalagem I., Botelho C., Alves-Vale C., Correia J. G., Jardim J. A. M., Domingos S. P., Baiao J. M., Rocha B. S., Lopes N. M. R. O., Jordao D. M., Angelo M. D., Caroco T., Vieira B. N., Silva A. G., Galvao D., Mora A., Bettencourt R., Quintela A. C., Alves D., Dias B., Costa C., Goncalves J. P., Valente P., Freire L., Saraiva R., Moreira M., Peixoto R., Serra M. L., Santos T. C., Lages R. R., Pimentel A., Martins M., Maciel J., Bartolo J., Fidalgo Antunes C., Cabral F., Brito Silva F., Dias Matos A., Santos M., Cunha R., Duarte M., Sousa M., Cunha M., Neves J., Monica I., Oliveira S., Ribeiro H., Ferreira M., Guimaraes N., Azevedo J., Louro H., Queiros T., Castro B., Fonseca S., Carvalho L., Torre A. P., Amado A., Leite M., Romano M., Gomes J. R., Monteiro R. G., Eiro F., Borges F., Simoes J., Botelho P., Cismasiu B., Romano J., Monteiro C., Silva M., Claro M., Almeida P., Cruz A., Vaz Pinto G., Sousa D., Costa Santos D., Silva A., Silva F., Almeida M. R., Parreira R., Faustino A., Medeiros N., Castro R., Soares B., Resendes M., Peyroteo M., Canotilho R., Correia A. M., Martins P. C., Machado N. D., Sa T. C., Bernardes F. M., Saraiva P., Almeida J., Mendes M., Fernandes V., Ribeiro A., Soares D., Capote H., Fialho G., Reia M., Pratas N., Costa J., Morais S., Miranda P., Cunha C., Sousa X., Amado F., Batista A., Seabra J., Praxedes V., Monteiro N., Martins I., Lamas M., Devesa H., Miranda J., Martins S. F., Cavadas D., Silva R., Pina S., Paixao I., Frade S., Guerreiro I., Tome M., Patrocinio S., Costa M., Rosete M., Senaratne R., Kakodkar P., Balasubramanian I., Hogan A., Al-Salihi A., Vyas V., Vedadi A., English C., Mohammed N., Dervan L., Kang S. J., Morrissey E., Compton M., Litvin A., Romanova E., Ponomarev N., Savchenko A., Meszarosova K., Zubowicz M., Suchan P. K., Gerstmeier J., Brazitikou E., Fytrou E., Celik M., Dubovsky M., Schmalenbeck J., Sautter S. C., Ceyran H., Panyko A., Jaich R., Fitchat N., De Lima H., Withey K., Piperidis A., Toyi Y., Nicolaides A., Brooks S., Jaffer T., Sparke A., Van Staden N., McDuling C. R., Claassen L., Van Vuuren S., Marx M., Kruger C., Weyers J., Lecler J., Nshalati Salvation M., Mathebula S., Chauke J., Mculu W., Ngwenya Z., Garcia Cardo J., Mora-Guzman I., Sancho Muriel J., de Andres Olabarria U., Casaval Cornejo L., Vicente Rodriguez I., Jimenez Escovar F., Calvo Fernandez M., Portugal Martinez A., Badiola Bergara I., Landaluce Olavarria A., del Pozo Andres E., Muriel P., Mestres N., Cuello E., Merichal M., Sierra J. E., Escoll J., Rufas M., Pinillos A. I., Ortega J., Cerdan C., Jimenez Vinas C., Alconchel F., Martinez Diaz J. M., Ruiz Manzanera J. J., Navarro Barrios A., Rodriguez Pedreno L., Garcia Moreno P., Garcia Gomez M., Rodrigues K., Abrisqueta J., Esteban Sinovas O., Fairen Oro C., Lopez Otero M., Samartin Toimil C., Primo Alvarez J. C., Rodriguez Fernandez L., Paniagua Garcia Senorans M., Figueroa Jimenez S., Livianos Arias-Camison P., Nieto Arranz J. M., Mateos Sexmero M. J., Diego Alonso E., Gonzalez Amor L., Claramonte Bellmunt O., Martinez Caballero J., Rubio-Perez I., Ramos Martin P., Mate Mate P., Marcano Chavez C., Ayllon H., Aguilar-Martinez M. M., Arroyo A., Segura-Sampedro J. J., Jeri-McFarlane S., Soldevila-Verdeguer C., Pineno-Flores C., Ambrona-Zafra D., Fernandez-Vega L., Gil-Catalan A., Craus-Miguel A., Pujol-Cano N., Sena-Ruiz F., Olmedo Moreno C., Pastor Idoate C., Negre Parra D., Soriano Liebana M. M., Campo Betancourth C. F., Sevila Mico S., Estevez Diz A. M., Martin-Balbuena R., Garcia-Vico A., Roman-Rando A., Sanchez-Galvez M. A., Bersabe-Alonso I. M., Vadillo-Bohorquez A., Bustamante Recuenco C., Calzada M. G., Recuenco C. B., Martin M. C., Licardie Bolanos R. E., Garcia Orozco J. J., Ferrusola Diaz D. A., Garcia Jimenez M. L., Castro Diez L., Mosquera Fernandez C., Fernandez P., Platero Diago J., Veras Lista M., Rifa Terricabras S., Butler Sanz L., Alberch Camprubi E., Rico Ferrandez M., Puig Lao E., De Pablo Miro M., Diaz Padillo A., Padilla Zegarra E. D., Franco M., Martinez A., Forero-Torres A., Alonso-Poza A., Dieguez B., Losada M., Gilsanz C., Alberdi San Roman I., Ramos Jimenez F. A., Perez Ortega A., Trujillo Barbadillo A., Romero Pujana E., Fernandez Illera M. V., Salvador Roses H., Delisau Puig O., Castro A., Codony Bassols C., Fernandes N., Garcia Adamez J., Caula Freixa C., Gomez Romeu N., Merayo Alvarez M., Alonso Batanero E., Cifrian Canales I., Villarejo Campos P., Alberca-Paramo A., Alia Verdejo T., Canete-Manzanares J., Molina-Florez M., Garcia Hernandez L. C., Orozco Nunez S., Suarez-Sanchez M., Martin-Fernandez J., Estaire Gomez M., Lopes Moreira C. C., Gutierrez Rios R. D., Eizaguirre Ubegun M., Novo Sukia I., Uribe Isado M., Ibanez Alda M., Enriquez-Navascues J. M., Uriol Peralta P., Lima Pinto F., Nunez O'Sullivan S., Serrano Navidad M., Vivas Angeles P., Vives Figueras R., Baena Sanfeliu E., Campillo Alonso B., Alberich Prats M., Duran Arrocha J., Cornella Garceso N., Uribe Galeano C., Collado-Roura F., Ripolles-Melchor J., Garcea A., Gomez Facundo H., Troncoso Pereira P., Garcia J. M., Gil A., Giordano H. E., Perez Guarinos C. V., Blaser B., Imadalou L., Piazza G., Teixeira H., Pittet O., Gaspar S., Gagliardi B., Haller M. L., Huot A., Yurdaor S. S., Alim Y. E., Binbuga M., Kurklu O., Ceylan C., Yilmaz S., Calar S. N., Yildirim N., Yavuz G., Biyiklioglu O., Kopac O., Baykan B., Abbasguliyev H., Mutlu V., Mahmoudi Y., Dossa S. A. A., Mizan S. R., Demirtas B., Cavus T., Yuksek A., Karabulut K., Uyanik A., Kargici K., Banaz T., Abdulrahman S. M. F., Yesilsancak M., Yanikoglu E., Karabulut A., Kuyumcu O. F., Kutluk F., Tunc E., Ozmen B. B., Kurtoglu G. K., Sel E. K., Isler V. C., Yilmaz B. S., Adiyaman C., Kara M., Demirkaya H. C., Korkmaz H. K., Pektas A. M., Mutlu D., Tiftik E., Aksoy A. B., Karagoz E., Sabanci R., Tumer S. S., Sarigul L., Aksoy B., Emiroglu B., Mollavelioglu B., Gereklioglu D., Guler M., Toprak S., Afsar H. B., Guler S. E., Alizade E., Aydin T., Yalcinkaya A., Erdem M., Kayacan S., Sahin C., Uysal M., Karakus K., Altiner S., Demirci Z. S., Eren E., Yavas M., Dogan H., Ozoglu F., Mazlum S. S., Yelkenci C., Baran T., Satilmisoglu M., Sahin A. Z., Kilinc A., Isik K., Kocer M. D., Guner B., Islek E. C., Tombul H. B., Boztug C. Y., Tinaz A., Yilmaz M., Karaman Y., Akin F. A., Dansuk S., Bascavus M., Kaya M., Kutlu B., Akyol C., Bilicen G., Yarenci E., Demiroglu Y., Sunal A., Cinar E. N., Tipi O. U., Benli G. E., Tasdelen I., Tura A., Ucar A., Ekci B., Bilgili A. C., Kiraz I. N., Aksoy H., Basak A., Karip B., Uslu O., Seker M. C., Erten V., Memis U., Kocak Z. B., Karapinar Y. E., Fakirullahoglu M., Koseoglu E., Yeni M., Uygur F. A., Kaya Y., Ozen D., Olmez M., Altintas E., Toklu R., Saricicek T., Isik A. E., Demirci K., Suresh G., Anbarasan J., Rehman S., Hu E., Timms S., Reynolds W., Hotchkies A., Misra V., Finch B. J., Philip Rajathasan T., Jeddy H., Kyaw H. A., Wong N., Bhahirathan Y., Donaldson C., Sequeira Campos M., Armitage M. N., Hussain A. S., Hardy B., Hassan Serry M. Y., Herron J., Thakrar C., Rojoa D., Yeap B., Iqbal Z., Rojoa D. M., Cabaleiro Barciela C., Ruddy C. M., Lindwe S., Qamar Y., Chuita S., James A., Bugelli M., Chechelnitskaya Y., Bylinski T., Findlay J. M., Skan O., Kind C., Tupper P., Van Rhee C., Honeyman S. I., Menon G., Sloper W., Burford C., Coey J., Akbari K., Whitehead T., Dimitriadis S., Marshall K., Flint E. J., Can B., Cesmeli E., Kus D., Kavar R. C., Cevlik A. D., Cengiz U., Turk E. G., Yilmaz I., Yumurtaci O., Emin A., Girit C., Yildirak M. K., Senyigit E., Guldag A., Soyleyici B., Aytin Y. E., Akay F. E., Iskan N. G., Mutlu B., Sunay A. O., Bell T., Limnatitou D., Gormley S., Taleongpong P., Patel V., Macgregor L., Amini S., Turner C., To N., Laurence N., Green C., Frostick R., Khera R., Povey M., Mahapatra S., Bradbury M., Osunronbi T., Tam L. Y. C., Khanan Kaabneh A., Lawther J., Fisher P., Tribedi T., Moosa A., Ramdin A., McGee F., Flanagan S., Tan Q. J., Anwar H., Clough R., Chrisp B., Cassels J., Cross G. W. V., Refalo A., Hadley R., McTighe A., Farrow F., Brodie A., Davis G., Shah D. R., Bowers C., Ng M. P. E., Wong R. T. W., Maese S., Tandon R., Gray M., Kumar A., Ciurleo C., Nyamali I., Hiremath S., Sinha S., Chowdhary M., Kirupananthan P., Boh Z. Y., Dass S., Soma A., Newton A., Hill M., Shafiq Y., Brkljac M., Martin H., McClarty C., Sanyal S., Alsaif A., Bhopal S., Muneeb F., Page O., Zeb E., Al-Azzawi A., McIntosh J., Vucicevic A., Hughes M., Brooks L., Fanibi B., Dixon M., Njoku P., Morris D., Jobson J., Trussell S., Chowdhury H., Alawode D. O. T., Udayachandran V., Alsoof D., Ekert J., Joseph N., Zulkefley N., Hunt G., Christodoulou T., Wright O., Soman S., Jamal M., Beqiri S., Borgas P., Pereira F., Browne S., Yiu J., Dworkin A., Mak J., Patrawala S., Milinkovic N., Schofield R., Chauhan M., Hartley L., Hind J., Heybourne A., Morgan H., Wickstone C., Panagiotou D., O'Connell E., Dean K., Iqbal R., Walsh L., Yu N., Rana N., Massie E., Foong J., Lee Y. J., Mijalkov D., Wells A., Bull N., Ajmera A., Warburton T., Morgan S., Mahmoud A., Schachtel M., Mikhail B., Fomin I., Mekaeil B., Jun H. J. S., Hengpoonthana R., Childs S., Ridgway S., Blefari N. D. A., Tam H., Puchalski N., Ngai C., Mackenzie J., Johnson N., Holmes M., Zuzek R., Saluja T., Gould T., Goh Y. K., Selvaraj T., Horne D., Borrow J. L., Campbell C., Cousins G., Jackson L., Maheepala K., Zhao S., Holden E., Tutt L., Thompson B., Collins H., Louie F., Buckland B., Smith D., Chong C., Chua T. H., Nayak C., Redmond J., Tan R. R., Gramlick M., Teh J. S., Ng S. Y., Britten-Jones P., Mohd Rosli R., Pham H. D. V., Harris M., Salibasic M., Pavlov V., Paycheva T., Lyulenina E., Kolev N., Boev B., Nguen D., Mitkov Y., Mitkov E., Vladova P., Dimitrov V., Gabarski A., Feradova H., Mladenov T., Pos M., Adel A., Sotona O., Bartos M., Amjad T., Maly O., Berec S., Hanusova M., Hurny M., Orhalmi J., Sorensen J. S., Chanut F., Magnin J., Schoning L., Simon S. C. S., Galata C., Karampinis I., Thawel T., Seckler A. M., Kerem C., Durdevic S., Herrle F., Artioli E., Giaccari S., Nevoso V., Schimera A., Marino S., Resta G., Ongaro D., Baronio G., Raimondo S., Casiraghi S., Salvadori R., Armellini A., Vulcano I., Bertilone E., Pintabona G., Viscosi F., Mazzeo C., Olivieri M., Belluco C., Antona A. D., Basso S., Frattalone M., Marino F., Carbone F., Incollingo P., Romano F. M., Anania M., Pulighe F., Cruccu A., Murru M. L., Massaiu C., Balestra F., Pazzona M., De Nisco C., Gusai G. 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L., Jelovskis I., Deksnis D., Bauermeister Potts O., Slimbajevs T., Ancans G., Dulskas A., Kuliavas J., Kavaliauskas P., Kavaliauskaite R., te Molder L., Tromp J., Matthee E., Tissen Y. M., Brinkhuis E., de Vries H. S., t Hart E., Beckers K., Bekker Y., Kakar S., van Smaalen T. C., Veen O. C., Dingemans S. A., van den Brink L. C., Vijgen G. H. E. J., van de Voort E. M. F., van der Pool A., van Rest K. L. C., Haak T., Gordinou de Gouberville M. C., Saleh S., Mens M. A., Hoeks E. M., Nieuwenhuizen S., Brandsma A. M., van Praag E. M., Westerduin E., Smit M. P. C. M., van der Lely S. J., de Ruiter A., Ribbers T., Aarts C. A. M., Tulek M. S., de Jonge J., Kocak S., Alqethami H. J., Constansia R., van Elst P. C., Tissink M. W., Azzahhafi J., Bofarid S., Kip M., Saleh W., Franssen S., Boon C. L., Franssen R. J. M., Romaen I., Jense M. T. F., D'Souza J., Pascoe R., Scott A., Stark E., Mulholland K., Lau W. K., Smith B., Adams S. I. B., Shah N., Ling E., Young J., Hawkins R., Jacobson A., Macfater H., Stanfield B., Henderson N., Chuang A., Maskill L., Ker H., Mouldey K., Hu R., Matthews C., Aitken E., Walker M., Winstanley J., Miguel I., Martins J., Cunha M. F., Melo J., Veiga D. N., Rachadell J., Amorim E., Vareda R., Roseira J., Americano M., Correia D., Capella V., Moinhos T., Costa F., Gil I., Morgado J., Varghese S., Boyle E., Aljohmani L., Alexander J., Graziadei V., McCaughey C., Jain A., O'Connor D. B., Ramanayake H., Sabnani R., Colon L. F., Bansal N., Stephens I., Tan R., Hoo M., Doherty G., Fenn S., Mulhare E., Walsh M., Leavey C., Costigan O., Griffin S., Dockry E., Khogali E., Aly A. K., McPhedran R., O'Gorman D., Vermeulen D., Gopaul A., Pentony A. R., Piong C. L., Nossier R., Hanna J., Sabir K., Eow S. Y., Ladak N., Boersma D., Kamath P. J., Soh T. B. W., Dyer A. H., Chee S. Y., Tan I. X. H., Kelliher A., Scanlon K., Adeusi L., Howarth N., McCawley N., O'Neill A., Jones M. R., Saleh R., Singh A., O'Dwyer N., Mana O. C., Gomez H., Riba L., Perez J., Centeno A., Ortega C., Ossola M. E., Camarero E., Martinez Illan M., Aranda Garcia L., Lazaro Cardona M., Montalvo Olmedo C., Izquierdo Moreno A., Cuenca Ramirez A., Margarida A., Pando B., Liquete Marin L., Perez Calle M., Ramos Cordero M. J., Sagredo Cuartango A., Sanchez E., Marcos Rodrigo A., Fernandez A., Curtis C., Bosch M., Triguero D., Bosch Ramirez M., De La Llave Serralvo A., Sanchez M. J., Martin-Borregon P., Quevedo A., Martinez J., Marin J. M., Rodriguez P., Esteban Avendano I., Jimenez Relimpio C., Lancho Lavilla P., Blanco Bartolome I., Gomez Cano I., Blasco Andres C., Abad-Motos A., Marinez-Hurtado E., Salvachua-Fernandez R., Muniesa C., Avelino L., Cholewa H., Sancho-Muriel J., Navasquillo M., Navio A., Abello D., De Jesus M., Alvarez E., Kefleyesus A., Bugmann A., Piotet L. M., Meijers L., Tonchev P., Tamosiunas A., Rottier S. J., Negoi I., Bernado I. 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S., Toma T., Wadood Q., Yip J., Charalambides M., Clave Llavall A., Williamson E., Bharwada Y., Zearmal S., Evans H., Panikkar M., de la Cruz G., Caplan J., Ainger E., Busti S., Cunliffe L., Flamini T., Gaffing S., Moorcroft C., Peter M., Simpson L., Stokes E., Stott G., Wilson J., York J., Yousaf A., Ruparelia A., Tanvir T., Soare C., Pang Y. L., Trotter J., Zaidi A., Thakrar V., Brown M., Goaman A., Hodgson B., Ijeomah A., Iroegbu U., Kaur G., Lowe C., Mahmood S., Sattar Z., Sen P., Szuman A., Abbas N., Anto N., Bhome R., Eccles L., Elliott J., Hughes E. J., Jones A., Karunatilleke A. S., Knight J. S., Manson C. C. F., Mekhail I., Michaels L., Noton T. M., Okenyi E., Reeves T., Yasin I. H., Pulickal P., Ahmed H., Parnell J., Lennock S., Ford V., Banfield D. A., Harris R., Mason-Apps C., Roe T., Sandhu J., Shafiq N., Stickler E., Tam J. P., Williams L. 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L., Porter T., Potluri S., Stechman M., Tate S., Thomas D., Walford B., Auld F., Bleakley A., Johnston S., Jones C., Khaw J., Milne S., O'Neill S., Singh K. K. R., Swan A., Thorley N., Yalamarthi S., Yin Z. D., Balian V., Bana R., Clark K., Livesey C., McLachlan G., Mohammad M., Pranesh N., Richards C., Ross F., Sajid M., Liversedge G., Carrington Z., Windebank J., Izzarina A., Akbani U., Craven J., Aldarragi A., Harding S., Millward A., Brooke M., Francombe J., Gresly J., Hutchinson S., Kerrigan K., Matthews E., Nur S., Parsons L., Sandhu A., Vyas M., White F., Zulkifli A., Zuzarte L., Shortland T. C., Bedford M., Al-Mousawi A., Arya J., Azam S., Azri Yahaya A., Gill K., Hallan R., Hathaway C., Leptidis I., McDonagh L., Mitrasinovic S., Mushtaq N., Pang N., Peiris G. B., Rinkoff S., Gopalan V., Midgen A., Khadka P., Cheng O., Taneja S., Manobharath N., Chan L., Christopher E., Gonzalez-Ciscar A., Graham C. J., Lim H., Paterson H. 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E., Sagnotta A., Di Cintio A., Gemini A., Trastulli S., De Luca M., Desiderio J., Gubbiotti F., Campagnaro T., Pedrazzani C., Turri G., Lazzarini E., Conti C., Ruzzenente A., Petrelli F., Marziali I., Mazzocato S., Vergari R., Piazzai F., Kubolli I., Aggiusti A., Paolucci A., Ortenzi M., Gallo G., Clerico G., De Santi G., Bitonti M. F., Trompetto M., Realis Luc A., Papandrea M., Cerra C., Pirillo M., Cravano S., Libri I., Laquatra N., Isabello A., De Luca E., Testa V., Morino M., Mistrangelo M., Sinibaldi G., Angelucci G. P., Scaramuzzo R., Larcinese A., Fioriti C., Picone E., Nardi M., Di Candido F., Spinelli A., Marco M., Bevilacqua M., Maroli A., Colombo F., Cigognini M., Zaffaroni G., Maffioli A., Colombo S., Bondurri A., Sampietro G., Foschi D., Perrone G., Bonati E., Aresu S., Saba A., Biancafarina A., Angelini M., Andolfi E., Miranda E., Scricciolo M., Provenza G., Cavallina G., Frezza B., Fontani A., Malatesti R., Pellicano G. A., Ceccarelli G., Canonico G., Falsetti E., Pagnanelli M., De Nardi P., Rosati R., Marcocci G., Vignali A., Quattromani R., Curletti G., Galleano R., Malerba M., Percivale A., Ghazouani O., Reggiani L., Spirito C., Bini R., de Manzoni Garberini A., Impellizzeri H., Moretto G., Bacchion M., Casaril A., Inama M., Creciun M., Vitali M., Cillara N., Mosino L., Peddis M., Melis S., De Donno G., Aru A. C., Loche G. A., Tutino R., Licari L., Campanella S., Profita G., Falco N., Rotolo G., Venturelli P., De Marco P., Marciano M., Picciariello A., Chetta N., Aquilino F., Papagni V., Coletta D., Cerasari S., Galiffa G., Lapolla P., Del Basso C., Cirillo B., De Toma G., Fazzi K., Bini S., De Padua C., Savino G., Finotti E., Ferrara F., Stella M., Gobatti D., Tamini N., Brenna R., Giani A., Tirotta F., Famularo S., Angrisani M., Ceresoli M., Talamo G., Sucameli F., Gennai A., Moggia E., Bianchi C., Bonfante P., Macina S., Feleppa C., Imperatore M., Berti S., Parini D., Lanari J., Giamundo P., Lo Conte A., Pagano G., Manigrasso M., Danzi M., Amato R., Anastasio L., Mastella F., Basile R., Peltrini R., Marra E., Luglio G., Giglio M., Anoldo P., Vertaldi S., Grimaldi L., Tammaro N., Ripetti V., D'Alessio R., Benvenuto D., Pesce A., Menduni N., Giudicissi R., Zalla T., Baraghini M., Romoli L., Calussi M., Vellei S., Genzano C., Feroci F., Vita M., Giani I., Goldin E., Ciccioli E., Galgano A., Zuin M., Bettella A., Barina A., Vendramin E., Palano G., Schiavone D., Rega D., La Manna V., Migliore G., Aversano A., Fares Bucci A., Belli A., Andriola V., Lafranceschina S., Gordini L., Erdas E., Podda F., Cappellacci F., Salaris C., Sanna S., Marcialis J., Longheu A., Foppa C., Coratti F., Montanelli P., Grandi S., Nelli T., Ben Khaled N., Cammelli F., Ferrini E., Billo M. E., Piccolo G., Romano S., Gaetano P., Pilotta F., Baldassarre L., Birindelli A., D'Errico U., Bianchini S., Ferrari C., Franceschi A., Caristo G., Ballarini Z., Romelli M., Ruggiero S., Percassi A., Milone M., De Rosa M., Pipitone Federico N. S., Molteni B., Magri Piccinini A., Tilocca P. L., Marrosu A. G., Scognamillo F., Pala C., Attene F., Carboni L., Ruggiu M. W., Gabbas G., Sancini G., Roggiani A., Balsamo F., Gori A., Cuicchi D., Vittori L., Piozzi G. N., Tringali D., Bevilacqua E., Panizzo V., Lauretta A., Poillucci G., Mulas S., Simcikas D., Samalavicius N. E., Nutautiene V., Zeromskas P., Jurgaitis J., Aliosin O., Slepavicius A., Eismontas V., Kybransiene M., Portelli L., Cachia C., Cefai C., Youssef Y., Degaetano D., Debono S., Sammut M., Cassar J., Sammut K., Andrejevic P., van Wijnbergen J. W. M., Dinger T. L., ten Doesschate S. F. H., van Dalen A. S. H. M., Looijen R. C., Becker M. A. J., Comert D., Stellingwerf M. E., Abdulrahman N., van den Bos D. D., Gruter A., Vroom Y., Voeten D. M., Feenstra T., de Roy van Zuidewijn D., Hansmann M., Nasimi B., Gerdsen M., Stijns R. C. H., Leow T. Y. S., Penningnieuwland G., Davids J., Medina Feliz J., Kuiper S. Z., Sluijpers N. R. F., van de Pas K. G. H., Pruijssers S. R., Molenaar C. J. L., Thomas G., Farik S., Chen S. Y., Kilpatrick K., Kim D. H., Ong H. I., Elliott B. M., Geneta V. P., Alsadat R., Cherry R., Chapman D. A., Singh N., Clucas A., Gatenby G., Kelly B., Ruppeldt P., McIntosh N. D., Li Y., Wilton S., McLaughlin S. J. P., Kearney J., Sprosen H., Kerckhoffs P., Kandelaki H., Welman D., Coulter J., Morreau M., Li E., Rankin A., Winders J., Skipworth C., Peng S. L., Campbell S., Lim Y. K., Yassaie S. S., Dixon S., Yassaie S., Murray M., Haran C., Koh S., Wilms H., Dalzell F., Tewhaiti-Smith J., Kader T., Yam S. T., Dahya D., Hardie Boys M., Fleischl W., Desmond B., Tan J., Skavysh A., Castro J., Orelhas L., Santos J., Pacheco A., Rocha A. F., Jervis M. J., Pedro V., Paixao V., Guerreiro A., Melo D., Laranjeira A., Machado A., Horta V., Rocha-Melo M., Patricio J., Pereira M., Lima R., Cinza A. M., Oliveira J., Velez C., Senhorinho R., Catarino S., Aveiro D., Couto M., Loureiro A. R., Neves-Marques C., Louro T., Morgado M., Ferreira A. S., Alves M., Oliveira N., Lerias R., Estalagem I., Botelho C., Alves-Vale C., Correia J. G., Jardim J. A. M., Domingos S. P., Baiao J. M., Rocha B. S., Lopes N. M. R. O., Jordao D. M., Angelo M. D., Caroco T., Vieira B. N., Silva A. G., Galvao D., Mora A., Bettencourt R., Quintela A. C., Alves D., Dias B., Costa C., Goncalves J. P., Valente P., Freire L., Saraiva R., Moreira M., Peixoto R., Serra M. L., Santos T. C., Lages R. R., Pimentel A., Martins M., Maciel J., Bartolo J., Fidalgo Antunes C., Cabral F., Brito Silva F., Dias Matos A., Santos M., Cunha R., Duarte M., Sousa M., Cunha M., Neves J., Monica I., Oliveira S., Ribeiro H., Ferreira M., Guimaraes N., Azevedo J., Louro H., Queiros T., Castro B., Fonseca S., Carvalho L., Torre A. P., Amado A., Leite M., Romano M., Gomes J. R., Monteiro R. G., Eiro F., Borges F., Simoes J., Botelho P., Cismasiu B., Romano J., Monteiro C., Silva M., Claro M., Almeida P., Cruz A., Vaz Pinto G., Sousa D., Costa Santos D., Silva A., Silva F., Almeida M. R., Parreira R., Faustino A., Medeiros N., Castro R., Soares B., Resendes M., Peyroteo M., Canotilho R., Correia A. M., Martins P. C., Machado N. D., Sa T. C., Bernardes F. M., Saraiva P., Almeida J., Mendes M., Fernandes V., Ribeiro A., Soares D., Capote H., Fialho G., Reia M., Pratas N., Costa J., Morais S., Miranda P., Cunha C., Sousa X., Amado F., Batista A., Seabra J., Praxedes V., Monteiro N., Martins I., Lamas M., Devesa H., Miranda J., Martins S. F., Cavadas D., Silva R., Pina S., Paixao I., Frade S., Guerreiro I., Tome M., Patrocinio S., Costa M., Rosete M., Senaratne R., Kakodkar P., Balasubramanian I., Hogan A., Al-Salihi A., Vyas V., Vedadi A., English C., Mohammed N., Dervan L., Kang S. J., Morrissey E., Compton M., Litvin A., Romanova E., Ponomarev N., Savchenko A., Meszarosova K., Zubowicz M., Suchan P. K., Gerstmeier J., Brazitikou E., Fytrou E., Celik M., Dubovsky M., Schmalenbeck J., Sautter S. C., Ceyran H., Panyko A., Jaich R., Fitchat N., De Lima H., Withey K., Piperidis A., Toyi Y., Nicolaides A., Brooks S., Jaffer T., Sparke A., Van Staden N., McDuling C. R., Claassen L., Van Vuuren S., Marx M., Kruger C., Weyers J., Lecler J., Nshalati Salvation M., Mathebula S., Chauke J., Mculu W., Ngwenya Z., Garcia Cardo J., Mora-Guzman I., Sancho Muriel J., de Andres Olabarria U., Casaval Cornejo L., Vicente Rodriguez I., Jimenez Escovar F., Calvo Fernandez M., Portugal Martinez A., Badiola Bergara I., Landaluce Olavarria A., del Pozo Andres E., Muriel P., Mestres N., Cuello E., Merichal M., Sierra J. E., Escoll J., Rufas M., Pinillos A. I., Ortega J., Cerdan C., Jimenez Vinas C., Alconchel F., Martinez Diaz J. M., Ruiz Manzanera J. J., Navarro Barrios A., Rodriguez Pedreno L., Garcia Moreno P., Garcia Gomez M., Rodrigues K., Abrisqueta J., Esteban Sinovas O., Fairen Oro C., Lopez Otero M., Samartin Toimil C., Primo Alvarez J. C., Rodriguez Fernandez L., Paniagua Garcia Senorans M., Figueroa Jimenez S., Livianos Arias-Camison P., Nieto Arranz J. M., Mateos Sexmero M. J., Diego Alonso E., Gonzalez Amor L., Claramonte Bellmunt O., Martinez Caballero J., Rubio-Perez I., Ramos Martin P., Mate Mate P., Marcano Chavez C., Ayllon H., Aguilar-Martinez M. M., Arroyo A., Segura-Sampedro J. J., Jeri-McFarlane S., Soldevila-Verdeguer C., Pineno-Flores C., Ambrona-Zafra D., Fernandez-Vega L., Gil-Catalan A., Craus-Miguel A., Pujol-Cano N., Sena-Ruiz F., Olmedo Moreno C., Pastor Idoate C., Negre Parra D., Soriano Liebana M. M., Campo Betancourth C. F., Sevila Mico S., Estevez Diz A. M., Martin-Balbuena R., Garcia-Vico A., Roman-Rando A., Sanchez-Galvez M. A., Bersabe-Alonso I. M., Vadillo-Bohorquez A., Bustamante Recuenco C., Calzada M. G., Recuenco C. B., Martin M. C., Licardie Bolanos R. E., Garcia Orozco J. J., Ferrusola Diaz D. A., Garcia Jimenez M. L., Castro Diez L., Mosquera Fernandez C., Fernandez P., Platero Diago J., Veras Lista M., Rifa Terricabras S., Butler Sanz L., Alberch Camprubi E., Rico Ferrandez M., Puig Lao E., De Pablo Miro M., Diaz Padillo A., Padilla Zegarra E. D., Franco M., Martinez A., Forero-Torres A., Alonso-Poza A., Dieguez B., Losada M., Gilsanz C., Alberdi San Roman I., Ramos Jimenez F. A., Perez Ortega A., Trujillo Barbadillo A., Romero Pujana E., Fernandez Illera M. V., Salvador Roses H., Delisau Puig O., Castro A., Codony Bassols C., Fernandes N., Garcia Adamez J., Caula Freixa C., Gomez Romeu N., Merayo Alvarez M., Alonso Batanero E., Cifrian Canales I., Villarejo Campos P., Alberca-Paramo A., Alia Verdejo T., Canete-Manzanares J., Molina-Florez M., Garcia Hernandez L. C., Orozco Nunez S., Suarez-Sanchez M., Martin-Fernandez J., Estaire Gomez M., Lopes Moreira C. C., Gutierrez Rios R. D., Eizaguirre Ubegun M., Novo Sukia I., Uribe Isado M., Ibanez Alda M., Enriquez-Navascues J. M., Uriol Peralta P., Lima Pinto F., Nunez O'Sullivan S., Serrano Navidad M., Vivas Angeles P., Vives Figueras R., Baena Sanfeliu E., Campillo Alonso B., Alberich Prats M., Duran Arrocha J., Cornella Garceso N., Uribe Galeano C., Collado-Roura F., Ripolles-Melchor J., Garcea A., Gomez Facundo H., Troncoso Pereira P., Garcia J. M., Gil A., Giordano H. E., Perez Guarinos C. V., Blaser B., Imadalou L., Piazza G., Teixeira H., Pittet O., Gaspar S., Gagliardi B., Haller M. L., Huot A., Yurdaor S. S., Alim Y. E., Binbuga M., Kurklu O., Ceylan C., Yilmaz S., Calar S. N., Yildirim N., Yavuz G., Biyiklioglu O., Kopac O., Baykan B., Abbasguliyev H., Mutlu V., Mahmoudi Y., Dossa S. A. A., Mizan S. R., Demirtas B., Cavus T., Yuksek A., Karabulut K., Uyanik A., Kargici K., Banaz T., Abdulrahman S. M. F., Yesilsancak M., Yanikoglu E., Karabulut A., Kuyumcu O. F., Kutluk F., Tunc E., Ozmen B. B., Kurtoglu G. K., Sel E. K., Isler V. C., Yilmaz B. S., Adiyaman C., Kara M., Demirkaya H. C., Korkmaz H. K., Pektas A. M., Mutlu D., Tiftik E., Aksoy A. B., Karagoz E., Sabanci R., Tumer S. S., Sarigul L., Aksoy B., Emiroglu B., Mollavelioglu B., Gereklioglu D., Guler M., Toprak S., Afsar H. B., Guler S. E., Alizade E., Aydin T., Yalcinkaya A., Erdem M., Kayacan S., Sahin C., Uysal M., Karakus K., Altiner S., Demirci Z. S., Eren E., Yavas M., Dogan H., Ozoglu F., Mazlum S. S., Yelkenci C., Baran T., Satilmisoglu M., Sahin A. Z., Kilinc A., Isik K., Kocer M. D., Guner B., Islek E. C., Tombul H. B., Boztug C. Y., Tinaz A., Yilmaz M., Karaman Y., Akin F. A., Dansuk S., Bascavus M., Kaya M., Kutlu B., Akyol C., Bilicen G., Yarenci E., Demiroglu Y., Sunal A., Cinar E. N., Tipi O. U., Benli G. E., Tasdelen I., Tura A., Ucar A., Ekci B., Bilgili A. C., Kiraz I. N., Aksoy H., Basak A., Karip B., Uslu O., Seker M. C., Erten V., Memis U., Kocak Z. B., Karapinar Y. E., Fakirullahoglu M., Koseoglu E., Yeni M., Uygur F. A., Kaya Y., Ozen D., Olmez M., Altintas E., Toklu R., Saricicek T., Isik A. E., Demirci K., Suresh G., Anbarasan J., Rehman S., Hu E., Timms S., Reynolds W., Hotchkies A., Misra V., Finch B. J., Philip Rajathasan T., Jeddy H., Kyaw H. A., Wong N., Bhahirathan Y., Donaldson C., Sequeira Campos M., Armitage M. N., Hussain A. S., Hardy B., Hassan Serry M. Y., Herron J., Thakrar C., Rojoa D., Yeap B., Iqbal Z., Rojoa D. M., Cabaleiro Barciela C., Ruddy C. M., Lindwe S., Qamar Y., Chuita S., James A., Bugelli M., Chechelnitskaya Y., Bylinski T., Findlay J. M., Skan O., Kind C., Tupper P., Van Rhee C., Honeyman S. I., Menon G., Sloper W., Burford C., Coey J., Akbari K., Whitehead T., Dimitriadis S., Marshall K., Flint E. J., Can B., Cesmeli E., Kus D., Kavar R. C., Cevlik A. D., Cengiz U., Turk E. G., Yilmaz I., Yumurtaci O., Emin A., Girit C., Yildirak M. K., Senyigit E., Guldag A., Soyleyici B., Aytin Y. E., Akay F. E., Iskan N. G., Mutlu B., Sunay A. O., Bell T., Limnatitou D., Gormley S., Taleongpong P., Patel V., Macgregor L., Amini S., Turner C., To N., Laurence N., Green C., Frostick R., Khera R., Povey M., Mahapatra S., Bradbury M., Osunronbi T., Tam L. Y. C., Khanan Kaabneh A., Lawther J., Fisher P., Tribedi T., Moosa A., Ramdin A., McGee F., Flanagan S., Tan Q. J., Anwar H., Clough R., Chrisp B., Cassels J., Cross G. W. V., Refalo A., Hadley R., McTighe A., Farrow F., Brodie A., Davis G., Shah D. R., Bowers C., Ng M. P. E., Wong R. T. W., Maese S., Tandon R., Gray M., Kumar A., Ciurleo C., Nyamali I., Hiremath S., Sinha S., Chowdhary M., Kirupananthan P., Boh Z. Y., Dass S., Soma A., Newton A., Hill M., Shafiq Y., Brkljac M., Martin H., McClarty C., Sanyal S., Alsaif A., Bhopal S., Muneeb F., Page O., Zeb E., Al-Azzawi A., McIntosh J., Vucicevic A., Hughes M., Brooks L., Fanibi B., Dixon M., Njoku P., Morris D., Jobson J., Trussell S., Chowdhury H., Alawode D. O. T., Udayachandran V., Alsoof D., Ekert J., Joseph N., Zulkefley N., Hunt G., Christodoulou T., Wright O., Soman S., Jamal M., Beqiri S., Borgas P., Pereira F., Browne S., Yiu J., Dworkin A., Mak J., Patrawala S., Milinkovic N., Schofield R., Chauhan M., Hartley L., Hind J., Heybourne A., Morgan H., Wickstone C., Panagiotou D., O'Connell E., Dean K., Iqbal R., Walsh L., Yu N., Rana N., Massie E., Foong J., Lee Y. J., Mijalkov D., Wells A., Bull N., Ajmera A., Warburton T., Morgan S., Mahmoud A., Schachtel M., Mikhail B., Fomin I., Mekaeil B., Jun H. J. S., Hengpoonthana R., Childs S., Ridgway S., Blefari N. D. A., Tam H., Puchalski N., Ngai C., Mackenzie J., Johnson N., Holmes M., Zuzek R., Saluja T., Gould T., Goh Y. K., Selvaraj T., Horne D., Borrow J. L., Campbell C., Cousins G., Jackson L., Maheepala K., Zhao S., Holden E., Tutt L., Thompson B., Collins H., Louie F., Buckland B., Smith D., Chong C., Chua T. H., Nayak C., Redmond J., Tan R. R., Gramlick M., Teh J. S., Ng S. Y., Britten-Jones P., Mohd Rosli R., Pham H. D. V., Harris M., Salibasic M., Pavlov V., Paycheva T., Lyulenina E., Kolev N., Boev B., Nguen D., Mitkov Y., Mitkov E., Vladova P., Dimitrov V., Gabarski A., Feradova H., Mladenov T., Pos M., Adel A., Sotona O., Bartos M., Amjad T., Maly O., Berec S., Hanusova M., Hurny M., Orhalmi J., Sorensen J. S., Chanut F., Magnin J., Schoning L., Simon S. C. S., Galata C., Karampinis I., Thawel T., Seckler A. M., Kerem C., Durdevic S., Herrle F., Artioli E., Giaccari S., Nevoso V., Schimera A., Marino S., Resta G., Ongaro D., Baronio G., Raimondo S., Casiraghi S., Salvadori R., Armellini A., Vulcano I., Bertilone E., Pintabona G., Viscosi F., Mazzeo C., Olivieri M., Belluco C., Antona A. D., Basso S., Frattalone M., Marino F., Carbone F., Incollingo P., Romano F. M., Anania M., Pulighe F., Cruccu A., Murru M. L., Massaiu C., Balestra F., Pazzona M., De Nisco C., Gusai G. P., Giannella A., Santangelo M., Frangella F., Magagnano D., Liberatore P., Rondelli F., Castagnoli G., Bartoli A., Bellochi R., Spaziani A., Conti D., Poponesi V., Trippetti M., Amicucci S., Tazza G., Procacci P., Giovannini F., Basile E., Moschetta G., Cosmi F., Romeo G., Gasparrini M., Virgilio E., Sparta C., Mura F. A., Barmina M., Lorettu A., Rettaroli C., Mastino G., Ruggiu G. V., Mura G. A., Perrone B. A., De Angelis M., Mereu A., Adamo V., Bianco C., Ricciardiello M., Campanaro C., Panaccio P., Esposito L. M., Di Mola F. F., D'Ascanio F., Pietroletti R., Di Marco F., Amico A., Schembari E., Puglisi S., Tuminello F., Figa F., Caiazzo A., Selvaggi L., Capozzolo A., Braccio B., Truskovs A., Bartnick A., Malcevs E., Machatschek M. J., Alm J., Lapsa S., Delorme M., Zeynalov F., Larnovskis J., Sauka J., Bodrov D., Gailumsis R., Wiemann A. M., Muller N. L., Jelovskis I., Deksnis D., Bauermeister Potts O., Slimbajevs T., Ancans G., Dulskas A., Kuliavas J., Kavaliauskas P., Kavaliauskaite R., te Molder L., Tromp J., Matthee E., Tissen Y. M., Brinkhuis E., de Vries H. S., t Hart E., Beckers K., Bekker Y., Kakar S., van Smaalen T. C., Veen O. C., Dingemans S. A., van den Brink L. C., Vijgen G. H. E. J., van de Voort E. M. F., van der Pool A., van Rest K. L. C., Haak T., Gordinou de Gouberville M. C., Saleh S., Mens M. A., Hoeks E. M., Nieuwenhuizen S., Brandsma A. M., van Praag E. M., Westerduin E., Smit M. P. C. M., van der Lely S. J., de Ruiter A., Ribbers T., Aarts C. A. M., Tulek M. S., de Jonge J., Kocak S., Alqethami H. J., Constansia R., van Elst P. C., Tissink M. W., Azzahhafi J., Bofarid S., Kip M., Saleh W., Franssen S., Boon C. L., Franssen R. J. M., Romaen I., Jense M. T. F., D'Souza J., Pascoe R., Scott A., Stark E., Mulholland K., Lau W. K., Smith B., Adams S. I. B., Shah N., Ling E., Young J., Hawkins R., Jacobson A., Macfater H., Stanfield B., Henderson N., Chuang A., Maskill L., Ker H., Mouldey K., Hu R., Matthews C., Aitken E., Walker M., Winstanley J., Miguel I., Martins J., Cunha M. F., Melo J., Veiga D. N., Rachadell J., Amorim E., Vareda R., Roseira J., Americano M., Correia D., Capella V., Moinhos T., Costa F., Gil I., Morgado J., Varghese S., Boyle E., Aljohmani L., Alexander J., Graziadei V., McCaughey C., Jain A., O'Connor D. B., Ramanayake H., Sabnani R., Colon L. F., Bansal N., Stephens I., Tan R., Hoo M., Doherty G., Fenn S., Mulhare E., Walsh M., Leavey C., Costigan O., Griffin S., Dockry E., Khogali E., Aly A. K., McPhedran R., O'Gorman D., Vermeulen D., Gopaul A., Pentony A. R., Piong C. L., Nossier R., Hanna J., Sabir K., Eow S. Y., Ladak N., Boersma D., Kamath P. J., Soh T. B. W., Dyer A. H., Chee S. Y., Tan I. X. H., Kelliher A., Scanlon K., Adeusi L., Howarth N., McCawley N., O'Neill A., Jones M. R., Saleh R., Singh A., O'Dwyer N., Mana O. C., Gomez H., Riba L., Perez J., Centeno A., Ortega C., Ossola M. E., Camarero E., Martinez Illan M., Aranda Garcia L., Lazaro Cardona M., Montalvo Olmedo C., Izquierdo Moreno A., Cuenca Ramirez A., Margarida A., Pando B., Liquete Marin L., Perez Calle M., Ramos Cordero M. J., Sagredo Cuartango A., Sanchez E., Marcos Rodrigo A., Fernandez A., Curtis C., Bosch M., Triguero D., Bosch Ramirez M., De La Llave Serralvo A., Sanchez M. J., Martin-Borregon P., Quevedo A., Martinez J., Marin J. M., Rodriguez P., Esteban Avendano I., Jimenez Relimpio C., Lancho Lavilla P., Blanco Bartolome I., Gomez Cano I., Blasco Andres C., Abad-Motos A., Marinez-Hurtado E., Salvachua-Fernandez R., Muniesa C., Avelino L., Cholewa H., Sancho-Muriel J., Navasquillo M., Navio A., Abello D., De Jesus M., Alvarez E., Kefleyesus A., Bugmann A., Piotet L. M., Meijers L., Tonchev P., Tamosiunas A., Rottier S. J., Negoi I., Bernado I. R., and Eftychiou S.
Abstract: Background: Postoperative acute kidney injury (AKI) is a common complication of major gastrointestinal surgery with an impact on short- and long-term survival. No validated system for risk stratification exists for this patient group. This study aimed to validate externally a prognostic model for AKI after major gastrointestinal surgery in two multicentre cohort studies. Methods: The Outcomes After Kidney injury in Surgery (OAKS) prognostic model was developed to predict risk of AKI in the 7 days after surgery using six routine datapoints (age, sex, ASA grade, preoperative estimated glomerular filtration rate, planned open surgery and preoperative use of either an angiotensin-converting enzyme inhibitor or an angiotensin receptor blocker). Validation was performed within two independent cohorts: a prospective multicentre, international study (‘IMAGINE’) of patients undergoing elective colorectal surgery (2018); and a retrospective regional cohort study (‘Tayside’) in major abdominal surgery (2011–2015). Multivariable logistic regression was used to predict risk of AKI, with multiple imputation used to account for data missing at random. Prognostic accuracy was assessed for patients at high risk (greater than 20 per cent) of postoperative AKI. Results: In the validation cohorts, 12.9 per cent of patients (661 of 5106) in IMAGINE and 14.7 per cent (106 of 719 patients) in Tayside developed 7-day postoperative AKI. Using the OAKS model, 558 patients (9.6 per cent) were classified as high risk. Less than 10 per cent of patients classified as low-risk developed AKI in either cohort (negative predictive value greater than 0.9). Upon external validation, the OAKS model retained an area under the receiver operating characteristic (AUC) curve of range 0.655–0.681 (Tayside 95 per cent c.i. 0.596 to 0.714; IMAGINE 95 per cent c.i. 0.659 to 0.703), sensitivity values range 0.323–0.352 (IMAGINE 95 per cent c.i. 0.281 to 0.368; Tayside 95 per cent c.i. 0.253 to 0.461), and specif
Published: 2022

37. Forecasting Shifts in Hoosiers’ Travel Demand and Behavior

Author: Verma, Rajat, Luo, Hao, Deodhar, Saloni, Ka, Eunhan, Chahine, Ricardo, Natu, Pallavi, Malhotra, Harshit, Polisetty, Vineeth, Thakkar, Dutt J., Ukkusuri, Satish V., Cai, Hua, Dunlop, Steven R., Iyer, Anath V., Gkritza, Konstantina, Verma, Rajat, Luo, Hao, Deodhar, Saloni, Ka, Eunhan, Chahine, Ricardo, Natu, Pallavi, Malhotra, Harshit, Polisetty, Vineeth, Thakkar, Dutt J., Ukkusuri, Satish V., Cai, Hua, Dunlop, Steven R., Iyer, Anath V., and Gkritza, Konstantina
Abstract: The changing landscape of transportation technology and traveler behavior, accelerated by recent events like COVID-19, has led to significant shifts in travel demand and vehicle miles traveled in Indiana. This study seeks to understand the long-term implications of these changes and their potential impact on passenger, freight, and micro-mobility movements across the state. To achieve this objective, this project focused on forecasting future transportation demand conditions and carrying out long-range scenario planning by accomplishing four tasks: forecasting travel demand shifts based on location-based data, evaluating medium-term inter- and intra-urban transportation demand shifts, forecasting county-level industry shifts using scenario-based growth models, and providing recommendations and guidance to the Indiana Department of Transportation (INDOT) based on the study results. Results offer improved planning for infrastructure investments and operations, the incorporation of emerging technologies into transportation planning processes, and an enhanced understanding of passenger and freight movements at the statewide and regional levels. Deliverables from this study include valuable tools and models that can help INDOT navigate potential transportation system changes and accommodate the evolving needs of the future.
Published: 2023

38. Economic Effect of Active Transportation Features and the Association Between the Healthcare Industry and Transportation

Author: Dunlop, Steven R., Ukkusuri, Satish, Thakkar, Dutt J., Mittal, Shagun, Patil, Utkarsh, Gala, Jainam, Brady, Thomas, Dunlop, Steven R., Ukkusuri, Satish, Thakkar, Dutt J., Mittal, Shagun, Patil, Utkarsh, Gala, Jainam, and Brady, Thomas
Abstract: The goal of this project is to help INDOT determine the economic effects of active transportation features, the impact of transportation infrastructure on the healthcare industry, and to explore a potential relationship between active transportation and healthcare. To capture the details thoroughly, the analysis was done at a macro and micro level. We identified relevant attributes based on existing studies and captured the county-level data for these attributes from public sources. A regression analysis was performed at the macro-level to understand relationships and trends. In the micro-view, the analysis aimed to investigate the impact of active transportation investments on business growth and the impact of transportation investments on trip patterns and healthcare growth at a granular level of ZIP Code Tabulation Areas (ZCTAs). Large-scale datasets were analyzed to extract key metrics, which were tested for changes due to investments in the region. A Difference in Differences (DID) model was used to analyze causal effects, and trends of individual ZCTAs were analyzed against their corresponding demographics. Insights were developed and recommendations were made to INDOT based on the analysis regarding macro trends and factors impacting the transportation features. Practical recommendations for transportation investments and their corresponding effects were provided to INDOT based on the micro analyses.
Published: 2023

39. Outcome of Stem Cell Transplantation in HTLV-1-Associated North American Adult T-Cell Leukemia/Lymphoma.

Author: Bazarbachi, Abdul-Hamid, Bazarbachi, Abdul-Hamid, Reef, Daniel, Narvel, Hiba, Patel, Riya, Al Hamed, Rama, Vikash, Sindhu, Neupane, Karun, Atalla, Eleftheria, Thakkar, Astha, Rahman, Shafia, Shah, Urvi, Adrianzen-Herrera, Diego, Quinn, Ryann, Zareef, Sumaira, Rabinovich, Emma, De Castro, Alyssa, Joseph, Felisha, Gillick, Kailyn, Mustafa, Jennat, Khatun, Fariha, Lombardo, Amanda, Townsend-Nugent, Latoya, Abreu, Michelly, Chambers, Nicole, Elkind, Richard, Shi, Yang, Wang, Yanhua, Derman, Olga, Gritsman, Kira, Steidl, Ulrich, Goldfinger, Mendel, Kornblum, Noah, Shastri, Aditi, Mantzaris, Ioannis, Bachier-Rodriguez, Liza, Shah, Nishi, Cooper, Dennis, Verma, Amit, Ye, Bihui Hilda, Janakiram, Murali, Sica, Roberto Alejandro, Bazarbachi, Abdul-Hamid, Bazarbachi, Abdul-Hamid, Reef, Daniel, Narvel, Hiba, Patel, Riya, Al Hamed, Rama, Vikash, Sindhu, Neupane, Karun, Atalla, Eleftheria, Thakkar, Astha, Rahman, Shafia, Shah, Urvi, Adrianzen-Herrera, Diego, Quinn, Ryann, Zareef, Sumaira, Rabinovich, Emma, De Castro, Alyssa, Joseph, Felisha, Gillick, Kailyn, Mustafa, Jennat, Khatun, Fariha, Lombardo, Amanda, Townsend-Nugent, Latoya, Abreu, Michelly, Chambers, Nicole, Elkind, Richard, Shi, Yang, Wang, Yanhua, Derman, Olga, Gritsman, Kira, Steidl, Ulrich, Goldfinger, Mendel, Kornblum, Noah, Shastri, Aditi, Mantzaris, Ioannis, Bachier-Rodriguez, Liza, Shah, Nishi, Cooper, Dennis, Verma, Amit, Ye, Bihui Hilda, Janakiram, Murali, and Sica, Roberto Alejandro
Abstract: Adult T-cell leukemia/lymphoma (ATLL) remains challenging to treat and has dismal outcome. Allogeneic stem-cell transplantation (allo-SCT) has promising results, but data remain scarce. In this single-center retrospective analysis of 100 patients with ATLL from north America (67 acute, 22 lymphomatous), 17 underwent allo-SCT and 5 autologous SCT (ASCT), with a median follow-up of 65 months. Post-transplant 3-years relapse incidence (RI) and non-relapse mortality (NRM) were 51% and 37%, respectively, and 3-year progression-free survival (PFS) and overall survival (OS) were 31% and 35%, respectively. ASCT 1-year RI was 80% compared to 30% in allo-SCT (p = 0.03). After adjusting for immortal-time bias, allo-SCT had significantly improved OS (HR = 0.4, p = 0.01). In exploratory multivariate analysis, patients achieving first complete response and Karnofsky score ≥ 90 had significantly better outcomes, as did Black patients, compared to Hispanics, who had worse outcome. In transplanted patients, 14 died within 2 years, 4 of which ASCT recipients. Our data are the largest ATLL transplant cohort presented to date outside of Japan and Europe. We show that allo-SCT, but not ASCT, is a valid option in select ATLL patients, and can induce long term survival, with 40% of patients alive after more than 5 years.
Published: 2023

40. A nutritional supplement containing zinc during preconception and pregnancy increases human milk zinc concentrations

Author: Han, Soo Min, Devaraj, Surabhi, Derraik, José G. B., Vickers, Mark H., Huang, Fang, Dubascoux, Stephane, Godfrey, Keith M., Chan, Shiao-Yng, Pang, Wei Wei, Thakkar, Sagar K., Cutfield, Wayne S., Grp, NiPPeR Study, Han, Soo Min, Devaraj, Surabhi, Derraik, José G. B., Vickers, Mark H., Huang, Fang, Dubascoux, Stephane, Godfrey, Keith M., Chan, Shiao-Yng, Pang, Wei Wei, Thakkar, Sagar K., Cutfield, Wayne S., and Grp, NiPPeR Study
Abstract: Introduction: During pregnancy and lactation minerals such as zinc are required to support maternal and infant health. Zinc is involved in various cellular processes, with requirements increasing in pregnancy and lactation. In the setting of a randomized trial, we investigated the effects on human milk (HM) zinc concentrations of a micronutrient-containing supplement including zinc in the intervention (but not control) group, started preconception and taken throughout pregnancy until birth. Additionally, we characterized longitudinal changes in HM concentrations of zinc and other minerals (calcium, copper, iodine, iron, magnesium, manganese, phosphorus, potassium, selenium, and sodium). Methods: HM samples were collected across 7 time points from 1 week to 12 months from lactating mothers from Singapore (n = 158) and New Zealand (n = 180). HM minerals were quantified using sector field inductively coupled plasma mass spectrometry. Potential intervention effects on HM mineral concentrations were assessed using linear mixed models with a repeated measures design and time-weighted area-under-the-curve analyses. Results: Over the first 3 months of lactation, HM zinc concentrations were 11% higher in the intervention group compared to the control group (p = 0.021). Higher HM zinc concentrations were most evident at 6 weeks of lactation. The intervention had no effect on HM concentrations of other minerals, which were not differently supplemented to the control and intervention groups. Temporal changes in HM minerals over 12 months of lactation were studied in the New Zealand mothers; HM zinc and copper concentrations progressively decreased throughout 12 months, while iron, potassium, sodium, and phosphorus decreased until 6 months then plateaued. HM calcium and magnesium initially increased in early lactation and iodine remained relatively constant throughout 12 months. HM manganese and selenium fell over the initial months of lactation, with a nadir at 6 months, and in
Published: 2023
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41. Systematic Review of Fathers' Attitudes toward their Children with Down Syndrome: A Lifespan Approach from Infancy to Midlife.

Author: Thakkar, Deepali and Thakkar, Deepali
Abstract: Background / Aim: Traditionally, research has focused more on mothers’ attitudes and their experiences with their children having Down Syndrome (DS). This study aims to identify various attitudes and perceptions of fathers toward their children with Down syndrome. Two research questions were formulated to further explore the aim. Method: Four databases were used for the search process and five peer-reviewed studies met the predefined inclusion and exclusion criteria. Data were extracted using the overall data of 519 fathers as participants from the selected studies. Results: A chronology comprising 5 primary categories with underlying themes was established. These categories reflect on different stages of a child's life, including infancy, middle childhood, adolescence, and middle adulthood. As well as other concerns of fathers such as gender roles, personal worries, and financial troubles were also identified. Additionally, the challenges and rewards of raising a child with DS were identified. Conclusions: Despite the difficulties, fathers considered several strategies for accepting and helping their children. Fathers generally had a good attitude toward their children. However, it was found that there needs to be more knowledge of DS in society. Lastly, practical implications, limitations, and future research directions are discussed.
Published: 2023

42. Pion screening mass at finite chemical potential

Author: Thakkar, Rishabh, Hegde, Prasad, Thakkar, Rishabh, and Hegde, Prasad
Abstract: We present a method to compute the responses of meson screening masses to the chemical potential by Taylor expanding the correlator using lattice QCD simulation. We start by comparing the free theory lattice results with the analytical expression. Then, using symmetry arguments, we obtain an expression for the correlator in a series of the chemical potential at finite temperature. Using this, we obtain the lowest order correction to the screening mass at a finite chemical potential for temperatures around 2.5 GeV. Our lattice analysis is limited to isoscalar chemical potential for the pseudoscalar channel. The calculations were performed using (2+1)-flavors of the Highly Improved Staggered Quark (HISQ/tree) action, with the ratio of the strange quark mass to the light quark mass $m_s/m_\ell=20$ corresponding to pion masses of 160 MeV., Comment: 18 pages, 15 figures; updated version of the paper
Published: 2023
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43. Robust and Secure Medical Image Watermarking for Edge-enabled e-Healthcare

Author: Singh, Priyanka, Jyothsna Devi, K, Thakkar, Hiren Kumar, Bilal, Muhammad, Nayyar, Anand, Kwak, Daehan, Singh, Priyanka, Jyothsna Devi, K, Thakkar, Hiren Kumar, Bilal, Muhammad, Nayyar, Anand, and Kwak, Daehan
Abstract: Advancements in networking technologies have enabled doctors to remotely diagnose and monitor patients using the Internet of Medical Things (IoMT), telemedicine, and edge-enabled healthcare. In e-healthcare, medical reports and patient records are typically outsourced to a server, which can make them vulnerable to unauthorized access and tampering. Therefore, it is crucial to ensure the authorization, security, confidentiality, and integrity of medical data. To address these challenges, this paper proposes a novel reversible watermarking approach with a high payload and low computational cost. First, the input medical image is divided into a Border region (BR) and a Non-Border region (NBR). The NBR region is upscaled using Neighbour Mean Interpolation (NMI) to ensure reversibility. The Electronic Patient Record (EPR) is encrypted using a pseudorandom key, which is generated adaptively from the host medical image and the Enigma machine. The encrypted EPR is then embedded in the medical image using NMI. Two levels of tamper detection (global and local) are performed at the receiver's end for higher accuracy. A Global Integrity Code is generated and embedded in BR using LSB embedding technique for global tamper detection. The experimental results show that the visual quality and robustness are both high (Avg. PSNR = 41.03 dB and Avg. SSIM = 0.99, NC = 0.99, and BER = 0.0019 calculated for 100 images). The subjective and objective experimental analysis indicates that the proposed scheme is highly secure and the computational cost is also low. The average embedding and extraction time (including embedding, encryption and decryption, extraction process respectively) is 0.88 s and 0.83 s. It is resistant to various image processing attacks. A comparison with some of the most recent popular schemes confirms the scheme's effectiveness.
Published: 2023

44. A Privacy-Preserving Framework Using Hyperledger Fabric for EHR Sharing Applications

Author: Thakkar, Vidhi, Shah, Vrushank, Thakkar, Vidhi, and Shah, Vrushank
Abstract: Electronic Health Records, or EHRs, include private and sensitive information of a patient. The privacy of personal healthcare data can be protected through Hyperledger Fabric, a permissioned blockchain framework. A few Hyperledger Fabric- integrated EHR solutions have emerged in recent years. However, none of them implements the privacy-preserving techniques of Hyperledger Fabric to make transactions anonymous or preserve the transaction data privacy during the consensus. Our proposed architecture is built on Hyperledger Fabric and its privacy-preserving mechanisms, such as Identity Mixer, Private Data Collections, Channels and Transient Fields to securely store and transfer patient-sensitive data while providing anonymity and unlinkability of transactions.
Published: 2023

45. Bidirectional associations between bullying victimization and likeability among indian adolescents

Author: Universidade de Santiago de Compostela. Departamento de Psicoloxía Clínica e Psicobioloxía, Maneiro Boo, Lorena, Geel, Mitch van, Thakkar, Niharika, Vedder, Paul, Universidade de Santiago de Compostela. Departamento de Psicoloxía Clínica e Psicobioloxía, Maneiro Boo, Lorena, Geel, Mitch van, Thakkar, Niharika, and Vedder, Paul
Abstract: Research suggests that well-liked adolescents are less likely to be victimized by peers whereas disliked adolescents are at an increased risk for bullying victimization. Yet, bidirectional relations between likeability and bullying victimization remain understudied, particularly in non-Western countries. The main objective of this study was to analyze the bidirectional associations between bullying victimization and likeability in a sample of Indian adolescents, using a multi-informant gender-based approach. The sample was composed of 1238 students, aged 11–16 (66.6% males), from nine schools in India. Two follow-ups were carried out, spaced three-months apart, resulting in a sample of 1006 students (72% males) in the third wave of study. Two cross-lagged panel models (CLPM) were computed separately for self- and peer-reported bullying victimization, and multiple group analyses were used to examine gender differences. The results showed a complex longitudinal interplay between victimization and likeability, which differed between boys and girls. In boys, likeability and victimization were bidirectionally related over time, with slight differences between self- and peer-reports. Among girls, only two significant relations emerged, suggesting that peer victimization could lead to rejection, and having more friends could put girls at risk for future victimization. These findings indicate that bullying victimization is a complex phenomenon in which peer acceptance and rejection play a different role for boys and girls in the Indian context
Published: 2023

46. Short-Term Treatment Outcomes of Brolucizumab in Patients with Neovascular Age-Related Macular Degeneration: A Multicentre Indian Real-World Evidence Study

Author: Chakraborty,Debdulal, Thakkar,Milan, Venkatesh,Ramesh, Roy,Sangeeta, Bhavsar,Maulik, Karcher,Helene, Chakraborty,Debdulal, Thakkar,Milan, Venkatesh,Ramesh, Roy,Sangeeta, Bhavsar,Maulik, and Karcher,Helene
Abstract: Debdulal Chakraborty,1 Milan Thakkar,2 Ramesh Venkatesh,3 Sangeeta Roy,4 Maulik Bhavsar,5 Helene Karcher6 1Disha Eye Hospital, Kolkata, West Bengal, India; 2Dr. Milanâs Retina Care Centre, Rajkot, Gujarat, India; 3Narayana Nethralaya, Bangalore, Karnataka, India; 4Susrut Eye Foundation and Research Centre, Kolkata, West Bengal, India; 5Novartis Healthcare Pvt. Ltd., Mumbai, Maharashtra, India; 6Novartis Pharma AG, Basel, SwitzerlandCorrespondence: Debdulal Chakraborty, Disha Eye Hospital, Kolkata, West Bengal, India, Email devdc@rediffmail.comObjective: To evaluate the short-term effectiveness and safety outcomes following brolucizumab treatment in patients with neovascular age-related macular degeneration (nAMD) as a part of real-world clinical practice in India.Methods: This was a retrospective, observational, multicentre study including patients (â¥ 50 years old) diagnosed with nAMD. Anonymized data of the patients receiving the first dose of brolucizumab intravitreal injection (IVI) who were either treatment-naÃ¯ve or previously treated with a single or a combination of other anti-VEGF IVIs were included. The present study reported the change in retinal fluid levels from baseline to month 3, best-corrected visual acuity (BCVA), central retinal thickness (CRT), and the number of injections received. The adverse events in the three months after brolucizumab treatment initiation were also monitored.Results: The study included 63 patients (65 eyes) from four study centres across India (mean age: 69.1 Â± 9.7 years). A total of 82 brolucizumab injections were administered during the 3 months of study duration, with 52/65 (80.0%) eyes receiving only 1 injection. Resolution of IRF, SRF, and PED was observed in 76.9%, 64.6%, and 67.7% of eyes, respectively. Further, a significant reduction in CRT was observed (baseline: 403.5 Â± 118.7 Î¼m; month 3: 308.3 Â± 73.8 Î¼m; p < 0.001), and BCVA also improved notably from 0.7 Â± 0.5 logMAR at baseline to 0.5 Â± 0.4 logMAR
Published: 2023

47. A semi-physical tire model using line contact

Author: Thakkar, Dhruv and Thakkar, Dhruv
Published: 2023

48. Linear Space Data Structures for Finite Groups with Constant Query-time

Author: Das, Bireswar, Kumar, Anant, Sharma, Shivdutt, Thakkar, Dhara, Das, Bireswar, Kumar, Anant, Sharma, Shivdutt, and Thakkar, Dhara
Abstract: A finite group of order $n$ can be represented by its Cayley table. In the word-RAM model the Cayley table of a group of order $n$ can be stored using $O(n^2)$ words and can be used to answer a multiplication query in constant time. It is interesting to ask if we can design a data structure to store a group of order $n$ that uses $o(n^2)$ space but can still answer a multiplication query in constant time. We design a constant query-time data structure that can store any finite group using $O(n)$ words where $n$ is the order of the group. Farzan and Munro (ISSAC 2006) gave an information theoretic lower bound of $\Omega(n)$ on the number of words to store a group of order $n$. Since our data structure achieves this lower bound and answers queries in constant time, it is optimal in both space usage and query-time. A crucial step in the process is essentially to design linear space and constant query-time data structures for nonabelian simple groups. The data structures for nonableian simple groups are designed using a lemma that we prove using the Classification Theorem for Finite Simple Groups (CFSG)., Comment: A preliminary version of this article appeared in the pro- ceedings of the 39th International Symposium on Theoretical Aspects of Computer Science (STACS 2022)
Published: 2023

49. OEKG: The Open Event Knowledge Graph

Author: Gottschalk, Simon, Kacupaj, Endri, Abdollahi, Sara, Alves, Diego, Amaral, Gabriel, Koutsiana, Elisavet, Kuculo, Tin, Major, Daniela, Mello, Caio, Cheema, Gullal S., Sittar, Abdul, Swati, Tahmasebzadeh, Golsa, Thakkar, Gaurish, Gottschalk, Simon, Kacupaj, Endri, Abdollahi, Sara, Alves, Diego, Amaral, Gabriel, Koutsiana, Elisavet, Kuculo, Tin, Major, Daniela, Mello, Caio, Cheema, Gullal S., Sittar, Abdul, Swati, Tahmasebzadeh, Golsa, and Thakkar, Gaurish
Abstract: Accessing and understanding contemporary and historical events of global impact such as the US elections and the Olympic Games is a major prerequisite for cross-lingual event analytics that investigate event causes, perception and consequences across country borders. In this paper, we present the Open Event Knowledge Graph (OEKG), a multilingual, event-centric, temporal knowledge graph composed of seven different data sets from multiple application domains, including question answering, entity recommendation and named entity recognition. These data sets are all integrated through an easy-to-use and robust pipeline and by linking to the event-centric knowledge graph EventKG. We describe their common schema and demonstrate the use of the OEKG at the example of three use cases: type-specific image retrieval, hybrid question answering over knowledge graphs and news articles, as well as language-specific event recommendation. The OEKG and its query endpoint are publicly available., Comment: The definitive version of this work was published in the Proceedings of the 2nd International Workshop on Cross-lingual Event-centric Open Analytics co-located with the 30th The Web Conference (WWW 2021)
Published: 2023

50. Why Is Public Pretraining Necessary for Private Model Training?

Author: Ganesh, Arun, Haghifam, Mahdi, Nasr, Milad, Oh, Sewoong, Steinke, Thomas, Thakkar, Om, Thakurta, Abhradeep, Wang, Lun, Ganesh, Arun, Haghifam, Mahdi, Nasr, Milad, Oh, Sewoong, Steinke, Thomas, Thakkar, Om, Thakurta, Abhradeep, and Wang, Lun
Abstract: In the privacy-utility tradeoff of a model trained on benchmark language and vision tasks, remarkable improvements have been widely reported with the use of pretraining on publicly available data. This is in part due to the benefits of transfer learning, which is the standard motivation for pretraining in non-private settings. However, the stark contrast in the improvement achieved through pretraining under privacy compared to non-private settings suggests that there may be a deeper, distinct cause driving these gains. To explain this phenomenon, we hypothesize that the non-convex loss landscape of a model training necessitates an optimization algorithm to go through two phases. In the first, the algorithm needs to select a good "basin" in the loss landscape. In the second, the algorithm solves an easy optimization within that basin. The former is a harder problem to solve with private data, while the latter is harder to solve with public data due to a distribution shift or data scarcity. Guided by this intuition, we provide theoretical constructions that provably demonstrate the separation between private training with and without public pretraining. Further, systematic experiments on CIFAR10 and LibriSpeech provide supporting evidence for our hypothesis.
Published: 2023

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